The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.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
Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.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
Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effec...Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effect of high-fat feeding on cardiac morphology and mitochondrial function,alongside the mitigating effects of voluntary exercise training.Methods Six-week-old male C57Bl/6 J mice commenced a high fat diet(HFD)or chow diet and were randomized to receive locked(sedentary)or unlocked(voluntary exercise training(VET))running wheels at 10 weeks of age.Mice were monitored until 30 weeks of age and euthanized for collection of tissues.Magnetic resonance imaging was performed to assess body composition,and echocardiography was performed to assess cardiac function.Results Compared with chow-fed animals,the HFD increased body weight and adiposity and decreased cardiolipins(CL)in the heart,which are required for maintaining adequate mitochondrial respiration.Importantly,VET reversed these effects and induced physiological cardiac hypertrophy.Cardiac mitochondrial respiratory chain analysis revealed decreased complexes II and IV activity following high fat feeding,while VET enhanced complex I activity,emphasizing the cardioprotective effect of exercise training in obesity.Conclusion This study uncovers mechanisms by which obesity and exercise impact cardiac mitochondrial health and suggests the mitochondria is a therapeutic target in obesity-related cardiovascular diseases.展开更多
Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen re...Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.展开更多
Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is re...Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.展开更多
Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photo...Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photosynthetic systems,ultimately curbing growth or causing cell death.While mitochondria possess inhouse antioxidant machinery,how non-mitochondrial systems contribute to mitochondrial redox homeostasis has remained unresolved.Laura F.DiGiovanni et al.demonstrate that peroxisomes directly protect mitochondria through contact-mediated ROS shuttling.This discovery extends the concept of organelle crosstalk beyond metabolic exchange to contact-mediated ROS flux,adding a system-level buffer against oxidative stress.Deep understanding and regulation of this pathway are highly significant for exploring how ROS coordinate plant stress responses,enhancing crop stress resistance and reducing extreme environment-induced oxidative damage.This may provide breeders and agronomists with a novel approach to develop stress-resistant traits.展开更多
Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and tr...Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.展开更多
Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characteri...Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characterization of the endosomallysosomal pathways supporting the endocytic tra fficking has provided invaluable information also into mitophagy signaling.展开更多
BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense r...BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense remains limited.In this study,we aimed to characterize neuronal oxidative damage as a key heatstroke pathological mechanism and assess the neuroprotective effects of nuclear factor E2-related factor 2(NRF2).METHODS:After developing in vivo and in vitro heatstroke models,we employed histological staining,cell viability and apoptosis assays,oxidative stress indicators determination,organelle ultrastructural observation,and molecular expression analysis to investigate the mechanisms of brain injury and changes in the NRF2 pathway following heatstroke.We pretreated mice and SH-SY5Y cells with tert-butylhydroquinone(TBHQ) to activate NRF2 expression.Furthermore,we utilized NRF2 knockout(KO) mice and NRF2 siRNA transfection to suppress NRF2 expression,thereby examining the effects of NRF2 both in vivo and in vitro.RESULTS:We found that heatstroke induced neuronal damage,elevated oxidative stress levels,and caused structural damage to both the mitochondria and the endoplasmic reticulum(ER).Notably,NRF2 activation was insufficient post-heatstroke.Pretreatment with TBHQ effectively activated the NRF2 signaling pathway and mitigated the resulting damage.In contrast,these injuries were exacerbated in NRF2 KO mice and SH-SY5Y cells transfected with NRF2 siRNA.CONCLUSION:This preliminary research shows that the NRF2 antioxidant signaling pathway exerts a protective effect against oxidative stress,mitigating both mitochondrial and ER structural damage in neuronal cells during heatstroke.Therefore,targeting the NRF2 pathway is a promising therapeutic strategy for heatstroke-induced neuronal injury.展开更多
The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors ...The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.展开更多
Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut...Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut and the central nervous system.More importantly,mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain.Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases.Mitochondria are essential for meeting the host’s substantial neuronal metabolic demands,maintaining excitability,and facilitating synaptic transmission.Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases.Therefore,this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration,as well as the existing potential therapeutic strategies for neurodegenerative disorders.These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases,and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases.However,this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases,such as Huntington’s disease and Multiple sclerosis,and the potential therapeutic strategies were translated into clinical trials,which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.展开更多
Tumor cells undergo metabolic reprogramming to adapt to rapid proliferation and harsh microenvironments,as evidenced by aerobic glycolysis.Mitochondria serve as key coordinators of this process.Under internal and envi...Tumor cells undergo metabolic reprogramming to adapt to rapid proliferation and harsh microenvironments,as evidenced by aerobic glycolysis.Mitochondria serve as key coordinators of this process.Under internal and environmental stress in tumors,mitochondria reprogram metabolism by balancing energy dynamics,redirecting metabolic routes,communicating via metabolites,and preserving the quality of mitochondria,thus supporting tumor cell survival.Traditional Chinese medicine(TCM)has a key role in modulating mitochondrial reprogramming in tumor cells,possibly disrupting metabolic pathways that are necessary for survival and proliferation.However,the underlying molecular signaling and cellular biological mechanisms need to be elucidated.In this review,we focused on the Key functions of mitochondria in adapting to tumor metabolic reprogramming are the focus of this review and recent advances in and regulatory mechanisms of TCM and nano-pharmaceutical formulations in maintaining mitochondrial homeostasis are discussed.These insights may help understand the role of mitochondria in the pathogenesis of metabolic diseases,such as cancer,and identify therapeutic targets.展开更多
Metabolism-associated fatty liver disease(MAFLD)is a spectrum of chronic liver diseases caused by the abnormal accumulation of fat in the liver,which is becoming increasingly serious with the rise in obesity rates wor...Metabolism-associated fatty liver disease(MAFLD)is a spectrum of chronic liver diseases caused by the abnormal accumulation of fat in the liver,which is becoming increasingly serious with the rise in obesity rates worldwide.Studies have shown that the interaction between lipid droplets and mitochondria plays an important role in the development and progression of MAFLD.In particular,peridroplet mitochondria(PDM),as a unique class of mitochondrial subpopulations,play a key function in lipid metabolism through spatial proximity and functional synergy.The current study revealed the functional heterogeneity of PDM from different tissue sources by optimizing PDM isolation techniques(e.g.,differential centrifugation combined with protease-assisted method),which provided a theoretical basis for targeting lipid droplet-mitochondrial interactions to intervene in MAFLD.Therefore,this paper reviews the morphology,function and isolation methods of PDM,as well as the relationship between lipid droplet-mitochondrial interactions and MAFLD,with the aim of promoting the development of MAFLD intervention strategies based on lipid droplet-mitochondrial interactions.展开更多
Mitochondria are vital organelles whose impairment leads to numerous metabolic disorders.Mitochondrial transplantation serves as a promising clinical therapy.However,its widespread application is hindered by the limit...Mitochondria are vital organelles whose impairment leads to numerous metabolic disorders.Mitochondrial transplantation serves as a promising clinical therapy.However,its widespread application is hindered by the limited availability of healthy mitochondria,with the dose required reaching up to 109 mitochondria per injection/patient.This necessitates sustainable and tractable approaches for producing high-quality human mitochondria.In this study,we demonstrated a highly efficient mitochondriaproducing strategy by manipulating mitobiogenesis and tuning organelle balance in human mesenchymal stem cells(MSCs).Utilizing an optimized culture medium(mito-condition)developed from our established formula,we achieved an 854-fold increase in mitochondria production compared to normal MSC culture within 15 days.These mitochondria were not only significantly expanded but also exhibited superior function both before and after isolation,with ATP production levels reaching 5.71 times that of normal mitochondria.Mechanistically,we revealed activation of the AMPK pathway and the establishment of a novel cellular state ideal for mitochondrial fabrication,characterized by enhanced proliferation and mitobiogenesis while suppressing other energy-consuming activities.Furthermore,the in vivo function of these mitochondria was validated in the mitotherapy in a mouse osteoarthritis model,resulting in significant cartilage regeneration over a 12-week period.Overall,this study presented a new strategy for the off-the-shelf fabrication of human mitochondria and provided insights into the molecular mechanisms governing organelle synthesis.展开更多
Ischemic heart disease(IHD)is associated with high morbidity and mortality rates.Reperfusion therapy is the best treatment option for this condition.However,reperfusion can aggravate myocardial damage through a phenom...Ischemic heart disease(IHD)is associated with high morbidity and mortality rates.Reperfusion therapy is the best treatment option for this condition.However,reperfusion can aggravate myocardial damage through a phenomenon known as myocardial ischemia/reperfusion(I/R)injury,which has recently gained the attention of researchers.Several studies have shown that Chinese herbal medicines and their natural monomeric components exert therapeutic effects against I/R injury.This review outlines the current knowledge on the pathological mechanisms through which mitochondria participate in I/R injury,focusing on the issues related to energy metabolism,mitochondrial quality control disorders,oxidative stress,and calcium.The mechanisms by which mitochondria mediate cell death have also been discussed.To develop a resource for the prevention and management of clinical myocardial I/R damage,we compiled the most recent research on the effects of Chinese herbal remedies and their monomer components.展开更多
Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved...Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.展开更多
Acute pancreatitis(AP)is a life-threatening inflammatory condition triggered by the premature activation of trypsin.The limited understanding of its underlying pathophysiology remains a key obstacle to the development...Acute pancreatitis(AP)is a life-threatening inflammatory condition triggered by the premature activation of trypsin.The limited understanding of its underlying pathophysiology remains a key obstacle to the development of targeted therapies.Mounting evidence now underscores mitochondrial dysfunction as a critical pathogenic driver in AP.Cellular mitochondrial dysfunction often precedes both cytokine release and trypsin activation,potentially serving as a primary initiator in the development and advancement of AP.Mitochondrial dysfunction is associated with calcium overload,inflammatory reactions,mitochondrial permeability transition pore opening,mitophagy damage,and other potential pathogenesis of pancreatic cell injury.Elucidating the impact of mitochondrial injury in AP may facilitate the development of innovative treatment approaches.This review provides a comprehensive and systematic analysis of the pivotal role of mitochondria in regulating pancreatic homeostasis,while evaluating emerging therapeutic strategies aimed at mitigating mitochondrial dysfunction.By integrating cuttingedge research findings,this work highlights the translational potential of these advancements in redefining diagnostic frameworks and optimizing therapeutic approaches for the management of AP.展开更多
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
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supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
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MAF is supported by an NHMRC Investigator Grant(APP1194141)Research in his laboratory was supported by project grants from the NHMRC(APP1042465,APP1041760,and APP1156511).
文摘Background Obesity is a risk factor for developing cardiometabolic disease.Exercise training is pivotal in the treatment of obesity and is associated with reduced cardiovascular mortality.This study examined the effect of high-fat feeding on cardiac morphology and mitochondrial function,alongside the mitigating effects of voluntary exercise training.Methods Six-week-old male C57Bl/6 J mice commenced a high fat diet(HFD)or chow diet and were randomized to receive locked(sedentary)or unlocked(voluntary exercise training(VET))running wheels at 10 weeks of age.Mice were monitored until 30 weeks of age and euthanized for collection of tissues.Magnetic resonance imaging was performed to assess body composition,and echocardiography was performed to assess cardiac function.Results Compared with chow-fed animals,the HFD increased body weight and adiposity and decreased cardiolipins(CL)in the heart,which are required for maintaining adequate mitochondrial respiration.Importantly,VET reversed these effects and induced physiological cardiac hypertrophy.Cardiac mitochondrial respiratory chain analysis revealed decreased complexes II and IV activity following high fat feeding,while VET enhanced complex I activity,emphasizing the cardioprotective effect of exercise training in obesity.Conclusion This study uncovers mechanisms by which obesity and exercise impact cardiac mitochondrial health and suggests the mitochondria is a therapeutic target in obesity-related cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(22007008,22178048).
文摘Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.
基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01 and 2023-PT330-01Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:82161138027。
文摘Background:Alzheimer's disease(AD)represents the most prevalent neurodegenerative disorder,with mitochondrial dysfunction being observed in both AD patients and mouse models.Nonetheless,further investigation is required to elucidate the pathogenic genes associated with AD and to develop early diagnostic methodologies centered on mitochondrial function.Methods:In this study,the dataset GSE132903 was retrieved from the GEO database,encompassing both non-demented(ND)control and AD samples.Through the combination of differential expression gene analysis,weighted gene co-expression network analysis,and intersection with mitochondrial database gene sets,four hub genes associated with AD were identified.These four hub genes were subsequently validated in APP/PS1 and 5xFAD mouse models using molecular biology techniques.Results:The hub genes identified through bioinformatics analysis include SYNJ2BP,VDAC1,NUBPL,and COX19.Within the GSE132903 dataset,the expression levels of SYNJ2BP,NUBPL,and COX19 were significantly elevated in the AD group compared to the non-demented(ND)group,whereas VDAC1 expression was reduced in the AD group relative to the ND group.Furthermore,in the hippocampus of APP/PS1 and 5xFAD mouse models,the expression patterns of SYNJ2BP and NUBPL were consistent with the bioinformatics analysis results.Conclusion:Hub genes identified here through bioinformatics and molecular biology may help early diagnosis of AD patients and may also help build new AD models to explore its pathogenesis.
基金funded from the Natural Science Foundation of Heilongjiang Province(LH2024C095,YQ2023B001)the China Postdoctoral Science Foundation(2024M751241)+3 种基金the National Key Laboratory of Green Pesticides(Central China Normal University)the earmarked fund for China Agricultural Research System(CARS170503)Heilongjiang Province Agriculture Research SystemEcological Agriculture 20231197Heilongjiang Province“Double First Class”Discipline Collaborative Innovation Achievement Project(LJGXCG2023-036).
文摘Reactive oxygen species(ROS)act as early messengers in plants exposed to drought,salinity,heat and other environmental challenges.Their timely removal is crucial.Unchecked ROS injure membranes,macromolecules and photosynthetic systems,ultimately curbing growth or causing cell death.While mitochondria possess inhouse antioxidant machinery,how non-mitochondrial systems contribute to mitochondrial redox homeostasis has remained unresolved.Laura F.DiGiovanni et al.demonstrate that peroxisomes directly protect mitochondria through contact-mediated ROS shuttling.This discovery extends the concept of organelle crosstalk beyond metabolic exchange to contact-mediated ROS flux,adding a system-level buffer against oxidative stress.Deep understanding and regulation of this pathway are highly significant for exploring how ROS coordinate plant stress responses,enhancing crop stress resistance and reducing extreme environment-induced oxidative damage.This may provide breeders and agronomists with a novel approach to develop stress-resistant traits.
文摘Objective:To investigate effect of oleanolic acid(OA)on atherosclerosis and its related mechanisms.Methods:Human umbilical vein endothelial cells(HUVECs)were injured by oxidized low-density lipoprotein for 24 h and treated with OA,and the levels of cell proliferation,migration,adhesion,and apoptosis were evaluated by BrdU staining,scratch healing assay,monocyte-endothelial cell adhesion assay and flow cytometry.The mice were fed with a high-fat diet to induce an atherosclerosis model,and treated with OA by gastric gavage.The mice were divided into the control group,the model group,and the OA administration group.The blood lipid and plaque formation in mice were detected.In addition,oxidative stress and mitochondrial structure and function changes in cells and mice were evaluated by transmission electron microscopy,JC-1 fluorescent probe,and Western blotting assays.The expression levels of proteins in the AMPK/Drp1 pathway were examined through Western blot.Results:OA markedly increased cell viability and migration rate of HUVECs,and decreased the adhesion rate of THP-1 cells and the apoptosis rate.OA significantly reduced serum lipid levels,such as total cholesterol and triglyceride,in mice and inhibited plaque formation in the aorta.OA also significantly increased the content of superoxide dismutase and catalase,alleviated mitochondrial damage,such as mitochondrial swelling and mitochondrial cristae reduction,reduced the number of mitochondria,increased adenosine triphosphate content,and significantly reduced p-Drp1(Ser616)/Drp1,MFF and FIS1 levels,increased p-AMPK/AMPK levels,activated AMPK,and then regulated DRP1 activity.Conclusions:OA activates AMPK,which in turn regulates the activity of DRP1 to restore normal mitochondrial dynamics and reduce atherosclerosis.
文摘Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characterization of the endosomallysosomal pathways supporting the endocytic tra fficking has provided invaluable information also into mitophagy signaling.
基金supported by the National Natural Science Foundation of China (No.82202432)the Guangzhou Science and Technology Plan Project (No.2023A04J2059,2024A03J0242)。
文摘BACKGROUND:The central nervous system is a critical target of severe heatstroke,with oxidative stress and multi-organelle damage being the key pathogenic mechanisms.However,research on endogenous antioxidant defense remains limited.In this study,we aimed to characterize neuronal oxidative damage as a key heatstroke pathological mechanism and assess the neuroprotective effects of nuclear factor E2-related factor 2(NRF2).METHODS:After developing in vivo and in vitro heatstroke models,we employed histological staining,cell viability and apoptosis assays,oxidative stress indicators determination,organelle ultrastructural observation,and molecular expression analysis to investigate the mechanisms of brain injury and changes in the NRF2 pathway following heatstroke.We pretreated mice and SH-SY5Y cells with tert-butylhydroquinone(TBHQ) to activate NRF2 expression.Furthermore,we utilized NRF2 knockout(KO) mice and NRF2 siRNA transfection to suppress NRF2 expression,thereby examining the effects of NRF2 both in vivo and in vitro.RESULTS:We found that heatstroke induced neuronal damage,elevated oxidative stress levels,and caused structural damage to both the mitochondria and the endoplasmic reticulum(ER).Notably,NRF2 activation was insufficient post-heatstroke.Pretreatment with TBHQ effectively activated the NRF2 signaling pathway and mitigated the resulting damage.In contrast,these injuries were exacerbated in NRF2 KO mice and SH-SY5Y cells transfected with NRF2 siRNA.CONCLUSION:This preliminary research shows that the NRF2 antioxidant signaling pathway exerts a protective effect against oxidative stress,mitigating both mitochondrial and ER structural damage in neuronal cells during heatstroke.Therefore,targeting the NRF2 pathway is a promising therapeutic strategy for heatstroke-induced neuronal injury.
基金supported by Fondi Ateneo grants funded by Sapienza University (#RM120172A3160B53) to EBfunds from Jerome-Lejeune Foundation (#1887-2019b) to EBthe European Union–Next Generation EU (Project ECS 0000024Rome Technopole,–CUP B83C22002820006, NRPMission 4 Component 2 Investment 1.5 to LRR)
文摘The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways,with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline.Insulin resistance impairs neuronal metabolism and synaptic function,fostering neurodegeneration as observed in Alzheimer’s disease and Down syndrome.Indeed,Down syndrome,characterized by the triplication of the APP gene,represents a valuable genetic model for studying early-onset Alzheimer’s disease and accelerated aging.Building on the link between metabolic dysfunctions and neurodegeneration,innovative strategies addressed brain insulin resistance as a key driver of cognitive decline.Intranasal insulin has shown promise in improving cognition in early Alzheimer’s disease and type 2 diabetes,supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration.However,insulin-based therapies risk desensitizing insulin signaling,potentially worsening the disease.Incretins,particularly glucagon-like peptide 1 receptor agonists,offer neuroprotective benefits by enhancing insulin sensitivity,metabolism,and synaptic plasticity while reducing oxidative distress and neuroinflammation.This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance,mitochondrial dynamics(including their roles in energy metabolism),and oxidative distress regulation,as these are pivotal in both Alzheimer’s disease and Down syndrome.By addressing these interconnected mechanisms,innovative treatments may emerge for both metabolic and neurodegenerative disorders.
基金supported by General Program of National Natural Science Foundation of China,No.82370986(to LAW)Shaanxi Provincial NaturalScience Foundation Key Project,No.2023-JC-ZD-56(to SS).
文摘Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut and the central nervous system.More importantly,mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain.Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases.Mitochondria are essential for meeting the host’s substantial neuronal metabolic demands,maintaining excitability,and facilitating synaptic transmission.Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases.Therefore,this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration,as well as the existing potential therapeutic strategies for neurodegenerative disorders.These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases,and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases.However,this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases,such as Huntington’s disease and Multiple sclerosis,and the potential therapeutic strategies were translated into clinical trials,which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.
基金supported by the National Natural Science Foundation of China(Grant no.81922030)International Cooperation Project of the Belt and Road(Grant no.20400750600)+1 种基金Construction Project of Shanghai TCM-Integrated Innovative Flagship Hospital[Grant nos.ZY(2021-2023)-0205-05 and ZXXT-202203]Shanghai Municipal Commission of Health and Family Plan(Grant no.201840056).
文摘Tumor cells undergo metabolic reprogramming to adapt to rapid proliferation and harsh microenvironments,as evidenced by aerobic glycolysis.Mitochondria serve as key coordinators of this process.Under internal and environmental stress in tumors,mitochondria reprogram metabolism by balancing energy dynamics,redirecting metabolic routes,communicating via metabolites,and preserving the quality of mitochondria,thus supporting tumor cell survival.Traditional Chinese medicine(TCM)has a key role in modulating mitochondrial reprogramming in tumor cells,possibly disrupting metabolic pathways that are necessary for survival and proliferation.However,the underlying molecular signaling and cellular biological mechanisms need to be elucidated.In this review,we focused on the Key functions of mitochondria in adapting to tumor metabolic reprogramming are the focus of this review and recent advances in and regulatory mechanisms of TCM and nano-pharmaceutical formulations in maintaining mitochondrial homeostasis are discussed.These insights may help understand the role of mitochondria in the pathogenesis of metabolic diseases,such as cancer,and identify therapeutic targets.
基金supported by National Key Research and Development Program of China(No.2023YFF0724803)National Science Foundation of China(No.82274424)+1 种基金General Project of Traditional Chinese Medicine Joint Special Project of Yunnan Provincial Department of Science and Technology in 2024(No.202401AZ070001-038)Scientific Research Fund Project of Yunnan Provincial Education Department(No.2025Y0634,No.2025Y0627).
文摘Metabolism-associated fatty liver disease(MAFLD)is a spectrum of chronic liver diseases caused by the abnormal accumulation of fat in the liver,which is becoming increasingly serious with the rise in obesity rates worldwide.Studies have shown that the interaction between lipid droplets and mitochondria plays an important role in the development and progression of MAFLD.In particular,peridroplet mitochondria(PDM),as a unique class of mitochondrial subpopulations,play a key function in lipid metabolism through spatial proximity and functional synergy.The current study revealed the functional heterogeneity of PDM from different tissue sources by optimizing PDM isolation techniques(e.g.,differential centrifugation combined with protease-assisted method),which provided a theoretical basis for targeting lipid droplet-mitochondrial interactions to intervene in MAFLD.Therefore,this paper reviews the morphology,function and isolation methods of PDM,as well as the relationship between lipid droplet-mitochondrial interactions and MAFLD,with the aim of promoting the development of MAFLD intervention strategies based on lipid droplet-mitochondrial interactions.
基金supported by the National Key Research and Development Program of China(2022YFA1106800)the National Natural Science Foundation of China(T2121004,82394441,92268203).
文摘Mitochondria are vital organelles whose impairment leads to numerous metabolic disorders.Mitochondrial transplantation serves as a promising clinical therapy.However,its widespread application is hindered by the limited availability of healthy mitochondria,with the dose required reaching up to 109 mitochondria per injection/patient.This necessitates sustainable and tractable approaches for producing high-quality human mitochondria.In this study,we demonstrated a highly efficient mitochondriaproducing strategy by manipulating mitobiogenesis and tuning organelle balance in human mesenchymal stem cells(MSCs).Utilizing an optimized culture medium(mito-condition)developed from our established formula,we achieved an 854-fold increase in mitochondria production compared to normal MSC culture within 15 days.These mitochondria were not only significantly expanded but also exhibited superior function both before and after isolation,with ATP production levels reaching 5.71 times that of normal mitochondria.Mechanistically,we revealed activation of the AMPK pathway and the establishment of a novel cellular state ideal for mitochondrial fabrication,characterized by enhanced proliferation and mitobiogenesis while suppressing other energy-consuming activities.Furthermore,the in vivo function of these mitochondria was validated in the mitotherapy in a mouse osteoarthritis model,resulting in significant cartilage regeneration over a 12-week period.Overall,this study presented a new strategy for the off-the-shelf fabrication of human mitochondria and provided insights into the molecular mechanisms governing organelle synthesis.
基金supported by the National Natural Science Foundation of China(Grant No.:82074235)the Central Universities in China(Grant No.:2023-JYB-JBQN-041)。
文摘Ischemic heart disease(IHD)is associated with high morbidity and mortality rates.Reperfusion therapy is the best treatment option for this condition.However,reperfusion can aggravate myocardial damage through a phenomenon known as myocardial ischemia/reperfusion(I/R)injury,which has recently gained the attention of researchers.Several studies have shown that Chinese herbal medicines and their natural monomeric components exert therapeutic effects against I/R injury.This review outlines the current knowledge on the pathological mechanisms through which mitochondria participate in I/R injury,focusing on the issues related to energy metabolism,mitochondrial quality control disorders,oxidative stress,and calcium.The mechanisms by which mitochondria mediate cell death have also been discussed.To develop a resource for the prevention and management of clinical myocardial I/R damage,we compiled the most recent research on the effects of Chinese herbal remedies and their monomer components.
文摘Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.
基金Supported by National Natural Science Foundation of China,No.8217030254.
文摘Acute pancreatitis(AP)is a life-threatening inflammatory condition triggered by the premature activation of trypsin.The limited understanding of its underlying pathophysiology remains a key obstacle to the development of targeted therapies.Mounting evidence now underscores mitochondrial dysfunction as a critical pathogenic driver in AP.Cellular mitochondrial dysfunction often precedes both cytokine release and trypsin activation,potentially serving as a primary initiator in the development and advancement of AP.Mitochondrial dysfunction is associated with calcium overload,inflammatory reactions,mitochondrial permeability transition pore opening,mitophagy damage,and other potential pathogenesis of pancreatic cell injury.Elucidating the impact of mitochondrial injury in AP may facilitate the development of innovative treatment approaches.This review provides a comprehensive and systematic analysis of the pivotal role of mitochondria in regulating pancreatic homeostasis,while evaluating emerging therapeutic strategies aimed at mitigating mitochondrial dysfunction.By integrating cuttingedge research findings,this work highlights the translational potential of these advancements in redefining diagnostic frameworks and optimizing therapeutic approaches for the management of AP.
