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,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
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
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
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as...The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in th...Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.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
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnose...BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.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
Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instea...Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.展开更多
Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical change...Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical changes in SCs.Nevertheless,the molecular mechanisms involved are still not fully understood.Melatonin is a classic antioxidant that can alleviate HS-induced male reproductive damage.However,the underlying molecular mechanisms by which melatonin mitigates damage to goat testicular SCs remain unclear and require further investigation.Results In this study,an in vivo heat stress model was established in goats.The results showed that HS exposure led to testicular injury,abnormal spermatogenesis and apoptosis of SCs.To elucidate the mechanism of HS-induced SC apoptosis,primary SCs were isolated and cultured from goat testes,then exposed to HS.HS exposure increased the production of reactive oxygen species(ROS),decreased adenosine triphosphate(ATP)synthesis,and reduced mitochondrial membrane potential in SCs.Additionally,HS increased the expression of mitochondrial fission proteins 1(FIS1)and dynamin-related protein 1(DRP1)while decreasing the expression of mitochondrial fusion proteins Mitofusin 1(MFN1),Mitofusin 2(MFN2),and optic atrophy 1(OPA1).This resulted in excessive mitochondrial fission and mitochondria-dependent apoptosis.Mdivi-1(DRP1 inhibitor)reduces mitochondria-dependent apoptosis by inhibiting excessive mitochondrial fission.Mitochondrial fission is closely related to mitophagy.HS activated upstream mitophagy but inhibited autophagic flux,disrupting mitophagy and exacerbating mitochondria-dependent apoptosis.Finally,the classical antioxidant melatonin was shown to reduce mitochondria-dependent apoptosis in SCs exposed to HS by decreasing ROS levels,restoring mitochondrial homeostasis,and normalizing mitophagy.Conclusions In summary,these findings indicated that the mechanism of HS-induced mitochondria-dependent apoptosis in SCs is mediated by hyperactivation of the ROS-DRP1-mitochondrial fission axis and inhibition of mitochondrial autophagy.Melatonin inhibited HS-induced mitochondria-dependent apoptosis in SCs by restoring mitochondrial homeostasis.This study enhances the understanding of the mechanisms through which heat stress triggers apoptosis and provides a vision for the development of drugs against HS by targeting mitochondria in goats.展开更多
G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,ta...G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.展开更多
Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In a...Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.展开更多
Background:Allergic rhinitis(AR)is a kind of immune disease mediated by Ig E.We are intrigued by the potential role of DEK proto-oncogene(DEK)in inflammation-related diseases.We investigated the effects and mechanisms...Background:Allergic rhinitis(AR)is a kind of immune disease mediated by Ig E.We are intrigued by the potential role of DEK proto-oncogene(DEK)in inflammation-related diseases.We investigated the effects and mechanisms of DEK in treating AR,aiming to identify potential new treatment targets for AR.Methods:The AR mouse model was induced by house dust mite(HDM)(1 mg/m L).HNEp Cs stimulated by HDM(1 mg/m L)were pretreated for 24 h with or without DEK lentivirus.The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting,ELISA,flow cytometry,real-time quantitative PCR,immunohistochemistry,HE staining,PAS staining,Diff staining,and immunofluorescence.Results:After DEK knockdown,the inflammatory response of AR mice was reduced.In addition,DEK deletion mitigated nasal tissue damage and mitochondrial division.Our further studies showed that DEK deletion or inhibition led to the down-regulation of Rho A activity and decreased phosphorylation of Ezrin and Drp1 proteins,and inhibited mitochondrial division.Overall,DEK deficiency mitigated AR by down-regulating Rho A/Ezrin/Drp1 pathway activity.Conclusion:DEK alleviates AR through Rho A/Ezrin/Drp1 signaling pathway,which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.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.
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.
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.
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 grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
基金supported by a grant from the Fund of Chengdu Medical College (CYZYB22-03)。
文摘The mechanism of cell damage during acute pancreatitis (AP) has not been fully elucidated, and there is still a lack of specific or effective treatments. Increasing evidence has implicated mitochondrial dysfunction as a key event in the pathophysiology of AP. Mitochondrial dysfunction is closely related to calcium (Ca^(2+)) overload, intracellular adenosine triphosphate depletion, mitochondrial permeability transition pore openings, loss of mitochondrial membrane potential, mitophagy damage and inflammatory responses. Mitochondrial dysfunction is an early triggering event in the initiation and development of AP,and this organelle damage may precede the release of inflammatory cytokines, intracellular trypsin activation and vacuole formation of pancreatic acinar cells. This review provides further insight into the role of mitochondria in both physiological and pathophysiological aspects of AP, aiming to improve our understanding of the underlying mechanism which may lead to the development of therapeutic and preventive strategies for AP.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金supported by the National Natural Science Foundation of China(Grant No.:82272749)the Natural Science Foundation of Liaoning Province,China(Grant No.:2022-MS-190).
文摘Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.
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.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
基金Supported by National Key Technology Research and Developmental Program of China,No.2022YFC2704400 and No.2022YFC2704405.
文摘BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.
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.
文摘Oncogenic viruses include both DNA and RNA viruses which contribute to cancer development by disrupting cellular regulation and interfering in the immune responses.These viruses do not directly cause cancer but instead integrate their genetic material into the host genome thus,affecting cell cycle and tumor suppression.This deregulation also leads to impaired immune function and promotes tumor progression by disrupting the removal of infected cells.Generally,innate immunity consists of two important members,including mitochondria and cell deaths,which impact each other as well.Due to the close correlation between viruses,cell death pathways(apoptosis,necroptosis,and pyroptosis),and mitochondria(mitochondrial antiviral-signaling protein and reactive oxygen species generation),targeting these immune system representatives may offer therapeutic strategies to control the progression of oncogenic viral infections.Some previous studies have covered the association of oncogenic viruses with mitochondria and cell death pathways,respectively,but mitochondria and cell death interact with each other,separately,and this interaction may play a role in the progression of cancer induced by oncogenic viruses.Hence,the purpose of this review is to discuss the relationship between cell death,mitochondria,and viral oncogenesis,focusing on the most surveyed oncogenic viruses’mechanisms of action.
基金supported by the National Key Research and Development Program of China(No.2022YFD1300200)Basic Research Program of Jiangsu Province(BK20220315)+1 种基金Key Research and Development Project in Shaanxi Province(No.2022QCY-LL-52,No.2024NC-ZDCYL-03-02)Core and Key technological breakthroughs Project in agriculture of Shanxi Province(No.2023NYGG005).
文摘Background Heat stress(HS)poses a significant threat to male goat reproduction.Sertoli cells(SCs)provide both structural and nutritional support necessary for germ cells.HS induces physiological and biochemical changes in SCs.Nevertheless,the molecular mechanisms involved are still not fully understood.Melatonin is a classic antioxidant that can alleviate HS-induced male reproductive damage.However,the underlying molecular mechanisms by which melatonin mitigates damage to goat testicular SCs remain unclear and require further investigation.Results In this study,an in vivo heat stress model was established in goats.The results showed that HS exposure led to testicular injury,abnormal spermatogenesis and apoptosis of SCs.To elucidate the mechanism of HS-induced SC apoptosis,primary SCs were isolated and cultured from goat testes,then exposed to HS.HS exposure increased the production of reactive oxygen species(ROS),decreased adenosine triphosphate(ATP)synthesis,and reduced mitochondrial membrane potential in SCs.Additionally,HS increased the expression of mitochondrial fission proteins 1(FIS1)and dynamin-related protein 1(DRP1)while decreasing the expression of mitochondrial fusion proteins Mitofusin 1(MFN1),Mitofusin 2(MFN2),and optic atrophy 1(OPA1).This resulted in excessive mitochondrial fission and mitochondria-dependent apoptosis.Mdivi-1(DRP1 inhibitor)reduces mitochondria-dependent apoptosis by inhibiting excessive mitochondrial fission.Mitochondrial fission is closely related to mitophagy.HS activated upstream mitophagy but inhibited autophagic flux,disrupting mitophagy and exacerbating mitochondria-dependent apoptosis.Finally,the classical antioxidant melatonin was shown to reduce mitochondria-dependent apoptosis in SCs exposed to HS by decreasing ROS levels,restoring mitochondrial homeostasis,and normalizing mitophagy.Conclusions In summary,these findings indicated that the mechanism of HS-induced mitochondria-dependent apoptosis in SCs is mediated by hyperactivation of the ROS-DRP1-mitochondrial fission axis and inhibition of mitochondrial autophagy.Melatonin inhibited HS-induced mitochondria-dependent apoptosis in SCs by restoring mitochondrial homeostasis.This study enhances the understanding of the mechanisms through which heat stress triggers apoptosis and provides a vision for the development of drugs against HS by targeting mitochondria in goats.
基金supported the Fund of Sichuan Provincial Department of Science and Technology(Grant No.:2024YFFK0393)the CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2019-I2M-5-004).
文摘G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all marketed drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respiration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alzheimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.
基金supported by the National Natural Science Foundation of China(Grant No.81922030)the International Cooperation Project of the Belt and Road(Grant No.20400750600)+1 种基金the Construction Project of Shanghai TCMintegrated Innovative Flagship Hospital[Grant No.ZY(2021-2023)-0205-05,ZXXT-202203]the Shanghai Municipal Commission of Health and Family Plan(Grant No.201840056).
文摘Objective:Lung cancer is the leading cause of cancer-related deaths worldwide.Chemotherapy is associated with side effects,such as damage to myeloid cells and a reduction in the number of immune cells in patients.In addition,tumor cells hijack the mitochondria of immune cells through tunnel nanotubes,thereby weakening immune ability.Methods:In this study the effects of direct mitochondria transplantation on cancer cell proliferation and chemotherapeutic sensitivity were determined,as well as anti-tumor immunity in in vitro and in vivo lung cancer models.Results:A combination of mitochondrial transplantation and cisplatin chemotherapy was shown for the first time to significantly improve immune infiltration of advanced non-small cell lung cancer(NSCLC)and overcome the shortcomings of cisplatin chemotherapy,including damage to myeloid cells and a reduction in the number of immune cells.Conclusions:The findings of the current study provide valuable recommendations for enhancing immune infiltration and augmenting anti-tumor efficacy during chemotherapy in advanced NSCLC.In addition,the findings support“mitochondrial transfer”as a novel paradigm in tumor treatment.
基金National Natural Science Foundation of China,Grant/Award Number:82260007 and 82260218The Department of Education of Jilin Province,(JJKH20240698KJ)+1 种基金Natural Science Research Foundation of Jilin Province for Sciences and Technology,Grant/Award Number:20210101215JC20240602100RC and 20240404025ZP。
文摘Background:Allergic rhinitis(AR)is a kind of immune disease mediated by Ig E.We are intrigued by the potential role of DEK proto-oncogene(DEK)in inflammation-related diseases.We investigated the effects and mechanisms of DEK in treating AR,aiming to identify potential new treatment targets for AR.Methods:The AR mouse model was induced by house dust mite(HDM)(1 mg/m L).HNEp Cs stimulated by HDM(1 mg/m L)were pretreated for 24 h with or without DEK lentivirus.The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting,ELISA,flow cytometry,real-time quantitative PCR,immunohistochemistry,HE staining,PAS staining,Diff staining,and immunofluorescence.Results:After DEK knockdown,the inflammatory response of AR mice was reduced.In addition,DEK deletion mitigated nasal tissue damage and mitochondrial division.Our further studies showed that DEK deletion or inhibition led to the down-regulation of Rho A activity and decreased phosphorylation of Ezrin and Drp1 proteins,and inhibited mitochondrial division.Overall,DEK deficiency mitigated AR by down-regulating Rho A/Ezrin/Drp1 pathway activity.Conclusion:DEK alleviates AR through Rho A/Ezrin/Drp1 signaling pathway,which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.
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.
