Himalayan snowcock Tetraogallus himalayensis are distributed in alpine and subalpine areas in China. We used mi- tochondrial DNA control-region data to investigate the origin and past demographic change in sixty-seven...Himalayan snowcock Tetraogallus himalayensis are distributed in alpine and subalpine areas in China. We used mi- tochondrial DNA control-region data to investigate the origin and past demographic change in sixty-seven Himalayan snowcock T. himalayensis. The fragments of 1155 nucleotides from the control region of mitochondrial DNA were sequenced, and 57 poly- morphic positions defined 37 haplotypes. A high level of genetic diversity was detected in all populations sampled and may be associated isolation of the mountains and habitat fragmentation and deterioration from Quaternary glaciations. In the phylogenetic tree, all haplotypes grouped into four groups： clade A （Kunlun Mountains clade）, clade B （Northern Qinghai-Tibetan Plateau clade）, clade C （Tianshan Mountains clade） and clade D （Kalakunlun Mountains clade）. We found a low level of gene flow and significant genetic differentiation among all populations. Based on divergence time we suggest that the divergence of Himalayan snowcock occurred in the middle Pleistocene inter-glaciation, and expansion occurred in the glaciation. Analysis of mtDNA D-loop sequences confirmed demographic population expansion, as did our non-significant mismatch distribution analysis. In conclusion, limited gene flow and a pattern of partial isolation phylogeographic was found in geographic populations of T. hima- layansis based on the analysis on mtDNA D-loop sequences [Current Zoology 57 （6）： 758-767, 2011].展开更多
Attempts are being made to domesticate the grasscutter (Thryonomys swinderianus) for commercial production in Sub-Saharan Africa to cater for the protein needs of the people and to satisfy the craving for bushmeat, th...Attempts are being made to domesticate the grasscutter (Thryonomys swinderianus) for commercial production in Sub-Saharan Africa to cater for the protein needs of the people and to satisfy the craving for bushmeat, thereby reducing habitat destruction through hunting. The objective of this study was to determine the genetic diversity of grasscutter populations in Ghana. DNA was extracted from roots of hair samples collected from 84 grasscutters from three agro-ecological zones in Ghana, namely Guinea Savanna (n = 17), Forest (n = 22), and Coastal Savanna (n = 45). Mitochondrial D-loop was sequenced and the diversity was determined across the zones. Out of 26 haplotypes found, 15 were obtained from Guinea Savanna, 7 from Forest and 13 from Coastal Savanna. Haplotype diversities were 0.978, 0.853 and 0.875 respectively for Guinea Savanna, Forest and Coastal Savanna zones. Analysis of molecular variance (AMOVA) revealed significant differentiation between Forest and Savanna populations (FST = 0.14, p 0.05). Network analysis indicated two clusters, one of which consisted of only Savanna haplotypes. Population neutrality tests showed that Forest and Coastal Savanna populations had been stable while the Guinea Savanna zone population had undergone an expansion (Fu’s FS = ‐7.132,展开更多
Primers based upon the mitochondrial genome sequences of Bos taurus were used to amplify and sequence the complete mitochondrial D-loop region of Jiulong yak(Poephagus grunniens).The results showed that the length of ...Primers based upon the mitochondrial genome sequences of Bos taurus were used to amplify and sequence the complete mitochondrial D-loop region of Jiulong yak(Poephagus grunniens).The results showed that the length of D-loop was 893 bp,with 87.4%homology to the Bos taurus D-loop sequence;there were 17 bp deletion.Using Ovis aries as an outgroup,the phylogeny of representative species of Bovinae(P.grunniens,P.mutus,Bos taurus,Bos indicus,Bison bison,Bison bonasus,and Bubalus bubalis)was analyzed.Among Bovinae,the sequence divergence between P.grunniens,P.mutus and American bison(Bison bison)was 6.2%-6.8%,which was less than that of Bos taurus and Bos indicus within Bos(10.0%-11.3%).Phylogenetic analysis found that P.grunniens,P.mutus and Bison bison clustered first of all,indicating there was higher genetic comparability among them than to that of Bos.Combining data from paleontology,morphology,and molecular biology,the present analysis supports the argument that Poephagus grunniens and Poephagus mutus should be classified as a distinct genus in Bovinae,that is Poephagus.展开更多
Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment ...Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.展开更多
Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
Hypoxia–ischemia plays a role in the physiological and pathological processes of various diseases and presents a common challenge for humans under extreme environmental conditions.Neurons are particularly sensitive t...Hypoxia–ischemia plays a role in the physiological and pathological processes of various diseases and presents a common challenge for humans under extreme environmental conditions.Neurons are particularly sensitive to hypoxia–ischemia,and prolonged exposure may lead to irreversible brain damage.The primary mechanisms underlying this damage include energy depletion,mitochondrial dysfunction,oxidative stress,inflammation,and apoptosis.Mitochondria serve as primary organelles for adenosine triphosphate(ATP)production,and mitochondrial dysfunction plays a crucial role in mediating hypoxic pathophysiological processes.Hypoxic–ischemic preconditioning(H/IPC)is an endogenous cellular protective mechanism that reduces the damage caused by lethal hypoxic stressors.In this review,we summarize the potential role of H/IPC and its protective effects on mitochondrial quality control and function.This perspective offers a new approach for treating diseases caused by hypoxia–ischemia.展开更多
Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortal...Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.展开更多
Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in t...Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca^(2+) homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR–RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis;attenuates calcium influx and enhances Ca^(2+) reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF;and improves CHF by rebalancing mitochondrial dynamics and autophagy.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Objective:Hepatocellular carcinoma(HCC)ranks among themost prevalentmalignant tumors globally.Metabolically associated fatty liver disease is a significant risk factor for HCC.Adiponectin,a key regulatory protein in g...Objective:Hepatocellular carcinoma(HCC)ranks among themost prevalentmalignant tumors globally.Metabolically associated fatty liver disease is a significant risk factor for HCC.Adiponectin,a key regulatory protein in glucolipid metabolism,presents potential as an anti-tumor target in HCC cells.The study focused on evaluating the anti-HCC properties of AdipoRon,an agonist of the adiponectin receptor.Method:Cell viability and proliferation were assessed using the cell counting kit-8 and colony formation assays,respectively.AdipoRon’s effect on HCC cell damage was evaluated via flow cytometry,apoptosis,and(lactate dehydrogenase)LDH assays.Mitochondrial function was evaluated by measuring mitochondrial membrane potential(MMP),ATP levels,and Complex I activity.Additionally,mitochondrial reactive oxygen species(ROS)and calcium(Ca^(2+))levelswere analyzed usingMitoSOXRed and Rhod-2 AM probes,respectively.Results:Our findings indicated that AdipoRon suppressed the proliferation of HCC cells and triggered apoptosis,with both effects being dose-dependent.Furthermore,AdipoRon caused a decrease in mitochondrial membrane potential,ATP levels,and Complex I activity,alongside the generation of mitochondrial ROS.Notably,AdipoRon disrupted intracellular Ca^(2+)homeostasis by causing mitochondrial Ca^(2+)overload due to release fromthe endoplasmic reticulum(ER).Additionally,AdipoRon promoted Ca^(2+)release from the ER by activating the PLC-IP3-IP3R pathway.The resulting mitochondrial Ca^(2+)overload enhances the anti-HCC effect when combined with chemotherapeutic drugs.Conclusions:Therefore,our study demonstrates thatAdipoRon promotesmitochondrial Ca^(2+)overload and apoptosis in HCC cells by activating the PLC-IP3-IP3R signaling pathway.AdipoRon has the potential to become an effective anti-HCC drug.展开更多
Background Hypoxia is a pervasive challenge in aquaculture that poses a significant threat to aquatic organisms.Since fish cannot synthesize vitamin A endogenously,it must be supplied through diet,and it plays a vital...Background Hypoxia is a pervasive challenge in aquaculture that poses a significant threat to aquatic organisms.Since fish cannot synthesize vitamin A endogenously,it must be supplied through diet,and it plays a vital role in supporting fish stress resistance.This study aimed to investigate the protective effects of VA on the gills of adult grass carp(Ctenopharyngodon idella)against hypoxia and to elucidate the underlying mechanisms.Methods Six experimental diets with graded VA levels(375,862,1,614,2,099,2,786,and 3,118 IU/kg)were fed to grass carp(initial weight:726±1.2 g)for 60 d.After the trial,24 fish per treatment were selected,divided equally into normoxic and hypoxic groups,fasted for 24 h,and then subjected to a 96-h acute hypoxic challenge.Results The results demonstrated that VA supplementation mitigated hypoxia-induced damage in gill tissue,as evidenced by histological examination.Furthermore,VA alleviated oxidative stress,as indicated by reduced levels of lactate(LD),lactate dehydrogenase(LDH),reactive oxygen species(ROS),protein carbonyl(PC),and malondialdehyde(MDA).Further investigations indicated that VA alleviated mitochondrial stress,potentially through suppressing the canonical UPR^(mt) axis while activating both the UPR^(mt) sirtuin axis and the UPRIMS/Erα axis.VA also modulated mitochondrial mass via multiple mechanisms,including the promotion of mitochondrial biogenesis,maintenance of dynamics by stimulating fusion and reducing fission,and inhibition of mitophagy.The suppression of mitophagy likely involved downregulating both the Pink1/Parkin-dependent pathway and the Hif1a-Bnip3 pathway.Taken together,these adaptations suggested an essential role for VA in preserving mitochondrial homeostasis.Based on the quadratic regression analysis of ROS and MDA levels from the hypoxic group,the estimated VA requirements for adult grass carp were 2,013 and 2,056 IU/kg diet,respectively.Conclusions In summary,this study provided the first evidence that VA conferred protective effects against hypoxiainduced gill damage in grass carp.展开更多
The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem ...The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo...Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.展开更多
Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,...Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).展开更多
The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The mai...The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy s...Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.展开更多
Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiven...Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwid...Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.展开更多
基金Acknowledgments Financial support was provided by the National Natural Science Foundation of China （No. 30530130）, Dr Start-up Fund Research of Qiongzhou Univer- sity （No. QYXB201009） and the Co-operation Fund Between University and Locality, Sanya （No. 2010YD22） for funding this research.
文摘Himalayan snowcock Tetraogallus himalayensis are distributed in alpine and subalpine areas in China. We used mi- tochondrial DNA control-region data to investigate the origin and past demographic change in sixty-seven Himalayan snowcock T. himalayensis. The fragments of 1155 nucleotides from the control region of mitochondrial DNA were sequenced, and 57 poly- morphic positions defined 37 haplotypes. A high level of genetic diversity was detected in all populations sampled and may be associated isolation of the mountains and habitat fragmentation and deterioration from Quaternary glaciations. In the phylogenetic tree, all haplotypes grouped into four groups： clade A （Kunlun Mountains clade）, clade B （Northern Qinghai-Tibetan Plateau clade）, clade C （Tianshan Mountains clade） and clade D （Kalakunlun Mountains clade）. We found a low level of gene flow and significant genetic differentiation among all populations. Based on divergence time we suggest that the divergence of Himalayan snowcock occurred in the middle Pleistocene inter-glaciation, and expansion occurred in the glaciation. Analysis of mtDNA D-loop sequences confirmed demographic population expansion, as did our non-significant mismatch distribution analysis. In conclusion, limited gene flow and a pattern of partial isolation phylogeographic was found in geographic populations of T. hima- layansis based on the analysis on mtDNA D-loop sequences [Current Zoology 57 （6）： 758-767, 2011].
文摘Attempts are being made to domesticate the grasscutter (Thryonomys swinderianus) for commercial production in Sub-Saharan Africa to cater for the protein needs of the people and to satisfy the craving for bushmeat, thereby reducing habitat destruction through hunting. The objective of this study was to determine the genetic diversity of grasscutter populations in Ghana. DNA was extracted from roots of hair samples collected from 84 grasscutters from three agro-ecological zones in Ghana, namely Guinea Savanna (n = 17), Forest (n = 22), and Coastal Savanna (n = 45). Mitochondrial D-loop was sequenced and the diversity was determined across the zones. Out of 26 haplotypes found, 15 were obtained from Guinea Savanna, 7 from Forest and 13 from Coastal Savanna. Haplotype diversities were 0.978, 0.853 and 0.875 respectively for Guinea Savanna, Forest and Coastal Savanna zones. Analysis of molecular variance (AMOVA) revealed significant differentiation between Forest and Savanna populations (FST = 0.14, p 0.05). Network analysis indicated two clusters, one of which consisted of only Savanna haplotypes. Population neutrality tests showed that Forest and Coastal Savanna populations had been stable while the Guinea Savanna zone population had undergone an expansion (Fu’s FS = ‐7.132,
文摘Primers based upon the mitochondrial genome sequences of Bos taurus were used to amplify and sequence the complete mitochondrial D-loop region of Jiulong yak(Poephagus grunniens).The results showed that the length of D-loop was 893 bp,with 87.4%homology to the Bos taurus D-loop sequence;there were 17 bp deletion.Using Ovis aries as an outgroup,the phylogeny of representative species of Bovinae(P.grunniens,P.mutus,Bos taurus,Bos indicus,Bison bison,Bison bonasus,and Bubalus bubalis)was analyzed.Among Bovinae,the sequence divergence between P.grunniens,P.mutus and American bison(Bison bison)was 6.2%-6.8%,which was less than that of Bos taurus and Bos indicus within Bos(10.0%-11.3%).Phylogenetic analysis found that P.grunniens,P.mutus and Bison bison clustered first of all,indicating there was higher genetic comparability among them than to that of Bos.Combining data from paleontology,morphology,and molecular biology,the present analysis supports the argument that Poephagus grunniens and Poephagus mutus should be classified as a distinct genus in Bovinae,that is Poephagus.
基金National Natural Science Foundation of China,Nos.81920108017(to YX),82401546(to HL)Jiangsu Province Key Medical Discipline,No.ZDXK202216(to YX)the Key Research and Development Program of Jiangsu Province of China,No.BE2020620(to YX).
文摘Microglia are the first immune cells that are activated in the brain following ischemic stroke.Mitochondrial dysfunction exacerbates microglia-mediated neuroinflammation post-stroke.Caspase activation and recruitment domain 19(CARD19)is involved in innate immune response and inflammatory response,which are also important functions of microglia.However,the role of CARD19 in microglial biology and ischemic stroke remains unknown.Here,we observed that CARD19 expression was significantly elevated in microglia in the penumbra after ischemic stroke via analyzing the spatial transcriptomic sequencing data of ischemic brain tissue,as well as in an in vitro model of microglial activation.Remarkably,conditional knockdown of Card19 in microglia promoted post-stroke neuroinflammation and worsened neurological outcomes in a mouse model of ischemic stroke.Mechanistically,we found that CARD19 localized to mitochondria and promoted the assembly of mitochondrial intermembrane bridge components,while CARD19 deficiency in microglia caused ultrastructural and functional damage to the mitochondrial cristae,leading to an exaggerated pro-inflammatory response.Thus,our findings suggest that preserving mitochondrial cristae,by targeting CARD19 could be a novel therapeutic strategy for ameliorating neuroinflammation post-stroke and decreasing the volume of the ischemic penumbra.
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
基金funded by the National Natural Science Foundation of China(Nos.82060337 and 82360272)the Natural Science Foundation of Inner Mongolia(2025MS08033)+1 种基金the Shenzhen Longgang District Economic and Technological Development Special Fund Medical,Health Technology Plan Project(LGKCYLWS2021000033,LGKCYLWS2023025)the Shenzhen Science and Technology Plan Project(Nos.JCYJ20220531092412028 and JCYJ20230807121306012).
文摘Hypoxia–ischemia plays a role in the physiological and pathological processes of various diseases and presents a common challenge for humans under extreme environmental conditions.Neurons are particularly sensitive to hypoxia–ischemia,and prolonged exposure may lead to irreversible brain damage.The primary mechanisms underlying this damage include energy depletion,mitochondrial dysfunction,oxidative stress,inflammation,and apoptosis.Mitochondria serve as primary organelles for adenosine triphosphate(ATP)production,and mitochondrial dysfunction plays a crucial role in mediating hypoxic pathophysiological processes.Hypoxic–ischemic preconditioning(H/IPC)is an endogenous cellular protective mechanism that reduces the damage caused by lethal hypoxic stressors.In this review,we summarize the potential role of H/IPC and its protective effects on mitochondrial quality control and function.This perspective offers a new approach for treating diseases caused by hypoxia–ischemia.
基金Instituto de Salud CarlosⅢCB16/10/00435(CIBERFES)(PID2022-142470OB-I00)from the Spanish Ministry of Innovation and Science+3 种基金PROMETEO(CIPROM/2022/56)de"Consellería de Educación,Universidades,y Empleo de la Generalitat Valenciana"EU Funded H2020-DIABFRAIL-LATAM(Ref:825546)Red EXERNET-RED DE EJERCICIO FISICO Y SALUD(RED2022-134800-T)Agencia Estatal de Investigacion(Ministerio de Ciencias e Innovación)funded by Generalitat Valenciana and co-financed with FEDER funds(OP FEDER of Comunitat Valenciana 2014–2020).A.G-G(FPU22/02539)and S.S-R(PREP2022-000563)received a predoctoral grant financed by the Spanish Ministry of Universities.
文摘Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
基金supported by the National Natural Science Foundation of China (No. 82374195)。
文摘Chronic heart failure(CHF) remains a global health challenge with limited therapeutic options. Mitochondrial dysfunction is a key pathological feature, and traditional Chinese medicine(TCM) shows unique potential in targeting this mechanism. Evidence from human and animal models of heart failure indicates that TCM can restore mitochondrial function by regulating mitochondrial Ca^(2+) homeostasis, oxidative stress, energy metabolism, mitochondrial dynamics, and mitophagy. TCM-based treatment of CHF offers notable clinical advantages, including improved therapeutic efficacy, enhanced cardiac function, and reduced incidence of major cardiovascular events. Experimental studies demonstrate that TCM decoctions and monomers modulate signaling pathways such as PPAR–RXRα, NF-κB, and PI3K/AKT to alleviate oxidative stress. TCM also increases AMPK activity via phosphorylation of PGC-1α, indirectly promoting mitochondrial biogenesis;attenuates calcium influx and enhances Ca^(2+) reuptake, thereby ameliorating myocardial mitochondrial dysfunction in CHF;and improves CHF by rebalancing mitochondrial dynamics and autophagy.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by the Research Fund of Anhui Institute of Translational Medicine(2023zhyx-C84)Natural Science Research Project of Anhui Higher Education Institutions(2024AH050804).
文摘Objective:Hepatocellular carcinoma(HCC)ranks among themost prevalentmalignant tumors globally.Metabolically associated fatty liver disease is a significant risk factor for HCC.Adiponectin,a key regulatory protein in glucolipid metabolism,presents potential as an anti-tumor target in HCC cells.The study focused on evaluating the anti-HCC properties of AdipoRon,an agonist of the adiponectin receptor.Method:Cell viability and proliferation were assessed using the cell counting kit-8 and colony formation assays,respectively.AdipoRon’s effect on HCC cell damage was evaluated via flow cytometry,apoptosis,and(lactate dehydrogenase)LDH assays.Mitochondrial function was evaluated by measuring mitochondrial membrane potential(MMP),ATP levels,and Complex I activity.Additionally,mitochondrial reactive oxygen species(ROS)and calcium(Ca^(2+))levelswere analyzed usingMitoSOXRed and Rhod-2 AM probes,respectively.Results:Our findings indicated that AdipoRon suppressed the proliferation of HCC cells and triggered apoptosis,with both effects being dose-dependent.Furthermore,AdipoRon caused a decrease in mitochondrial membrane potential,ATP levels,and Complex I activity,alongside the generation of mitochondrial ROS.Notably,AdipoRon disrupted intracellular Ca^(2+)homeostasis by causing mitochondrial Ca^(2+)overload due to release fromthe endoplasmic reticulum(ER).Additionally,AdipoRon promoted Ca^(2+)release from the ER by activating the PLC-IP3-IP3R pathway.The resulting mitochondrial Ca^(2+)overload enhances the anti-HCC effect when combined with chemotherapeutic drugs.Conclusions:Therefore,our study demonstrates thatAdipoRon promotesmitochondrial Ca^(2+)overload and apoptosis in HCC cells by activating the PLC-IP3-IP3R signaling pathway.AdipoRon has the potential to become an effective anti-HCC drug.
基金funded by the Sichuan Science and Technology Program(2024YFNH0016)the earmarked fund for CARS(CARS-45)+1 种基金the National Science Fund for Distinguished Young Scholars of China(32425056)the National Key R&D Program of China(2023YFD2400600)。
文摘Background Hypoxia is a pervasive challenge in aquaculture that poses a significant threat to aquatic organisms.Since fish cannot synthesize vitamin A endogenously,it must be supplied through diet,and it plays a vital role in supporting fish stress resistance.This study aimed to investigate the protective effects of VA on the gills of adult grass carp(Ctenopharyngodon idella)against hypoxia and to elucidate the underlying mechanisms.Methods Six experimental diets with graded VA levels(375,862,1,614,2,099,2,786,and 3,118 IU/kg)were fed to grass carp(initial weight:726±1.2 g)for 60 d.After the trial,24 fish per treatment were selected,divided equally into normoxic and hypoxic groups,fasted for 24 h,and then subjected to a 96-h acute hypoxic challenge.Results The results demonstrated that VA supplementation mitigated hypoxia-induced damage in gill tissue,as evidenced by histological examination.Furthermore,VA alleviated oxidative stress,as indicated by reduced levels of lactate(LD),lactate dehydrogenase(LDH),reactive oxygen species(ROS),protein carbonyl(PC),and malondialdehyde(MDA).Further investigations indicated that VA alleviated mitochondrial stress,potentially through suppressing the canonical UPR^(mt) axis while activating both the UPR^(mt) sirtuin axis and the UPRIMS/Erα axis.VA also modulated mitochondrial mass via multiple mechanisms,including the promotion of mitochondrial biogenesis,maintenance of dynamics by stimulating fusion and reducing fission,and inhibition of mitophagy.The suppression of mitophagy likely involved downregulating both the Pink1/Parkin-dependent pathway and the Hif1a-Bnip3 pathway.Taken together,these adaptations suggested an essential role for VA in preserving mitochondrial homeostasis.Based on the quadratic regression analysis of ROS and MDA levels from the hypoxic group,the estimated VA requirements for adult grass carp were 2,013 and 2,056 IU/kg diet,respectively.Conclusions In summary,this study provided the first evidence that VA conferred protective effects against hypoxiainduced gill damage in grass carp.
基金funded by the NIH Office of Research Infrastructure Programs(P40 OD010440)supported by the National Natural Science Foundation of China(82471893 and 82070913)+2 种基金Key discipline project of Hongkou District Health Commission(HKLCFC202403)Tongji Hospital Start-up Funding for Scientific Research(RCQD2301)Research fund from Shanghai Fourth People's Hospital(sykyqd01801,SYXKZT-2021-1001).
文摘The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
文摘Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.
基金funded by the“Instituto de Salud Carlos III”(PI 17-000134,PI 20-0155,PI23/00176)the“Diputaciode Lleida”(PP10601-PIRS2021)to MPO+2 种基金Also from the“Diputaciode Lleida”(PP10605-PIRS2021)the“Generalitat de Catalunya”:Agency for Management of University and Research Grants(2021SGR00990)to RPSupport was also received in the form of a FUNDELA Grant,“RedELA-Plataforma Investigacion”and the“Fundacio Miquel Valls”(Jack Van den Hoek donation)(to MPO)。
文摘Neurodegenerative diseases are chronic,age-related disorders characterized by a relentless,irreversible,and selective loss of neurons in motor,sensory,or cognitive systems(Gao et al.,2019).Despite their heterogeneity,a common pathological feature across many of these diseases is the accumulation of aggregate-prone proteins.Particularly,the cytoplasmic aggregation in neurons of the Transactive response DNA-binding protein 43(TDP-43).
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
文摘The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
基金supported by the National Natural Science Foundation of China,Nos.81701040(to HM),82071180(to HM),82271206(to TL),82171191(to YW),82371211(to YW)the Natural Science Foundation of Beijing,No.7212023(to HM)Key Subject of the Natural Science Foundation ofJiangsu Province for Colleges and Universities,No.23KJA320009(to YW).
文摘Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment.
基金supported by grants from the National Natural Science Foundation of China(81301128,81771500,82202789,82205065)the 2022 Suzhou Health Youth Backbone Talent“National Tutorial System”Training Project(Qngg2022024)+2 种基金the Science and Technology Project of Suzhou City of China(SKJYD2021195)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20220530165211026)the Postgraduate Research and Practice Innovation Program in Jiangsu Province(KYCX22_3157,KYCX24_3371,YCX25_3517).
文摘Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.
基金supported by Top Talent Support Program for young and middle-aged people of Wuxi Health Committee(Grant No.HB2023008)Top Medical Expert Team of Wuxi Taihu Talent Plan(Grant Nos.DJTD202106,GDTD202105 and YXTD202101)+2 种基金Medical Key Discipline Program ofWuxi Health.Commission(Grant Nos.ZDXK2021007 and CXTD2021005)Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee(Grant No.BJ2023090)Scientific Research Program of Wuxi Health Commission(Grant Nos.Z20210 and M202208).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)and chronic kidney disease(CKD)have shown a marked global increase in prevalence,placing a substantial burden on public health and healthcare systems worldwide.Epidemiological data demonstrate a significant overlap between these two conditions,with further evidence from research identifying common pathophysiological features,such as lipid metabolism dysregulation,disrupted energy balance,and chronic systemic inflammation.Mitochondria are central to the pathophysiology of both diseases.In addition to their role in energy production,mitochondria are involved in numerous critical cellular processes,including biosynthesis,lipid metabolism,oxidative phosphorylation,signal transduction,and apoptosis regulation.Mitochondrial dysfunction,characterized by increased reactive oxygen species,impaired adenosine triphosphate synthesis,disrupted mitophagy,and changes in mitochondrial morphology,is implicated in the progression of both MAFLDandCKD.Given the pivotal role of mitochondria in maintaining cellularmetabolism homeostasis,dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD.This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis.
