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
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
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
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
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
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
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
Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studie...Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC.This review covers the pathogenesis of IBD and CRC,focusing on mitochondrial dysfunction,and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function.Additionally,recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC,encompassing mitochondrial damage,release of mitochondrial DNA(mtDNA),and impairment of mitophagy,are thoroughly summarized.The review also provides a systematic overview of natural compounds(such as flavonoids,alkaloids,and diterpenoids),Chinese medicines,and intestinal microbiota,which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function.In the future,it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function,which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.展开更多
Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential fo...Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential for mitochondrial metabolism,functioning both as redox coenzymes and as signaling agents that help regulate cellular balance.Thus,while its major role is in energy production,NAD+is widely recognized as a metabolic cofactor and also serves as a substrate for various enzymes involved in cellular signaling,like sirtuins(SIRTs),poly(ADP-ribosyl)polymerases(PARPs),mono(ADP-ribosyl)transferases,and CD38.Sirtuins,a family of NAD+-dependent deacetylases,are critical in this regulatory network.SIRT3 removes acetyl groups from and enhances the activity of key enzymes that participate in fatty acid breakdown,the tricarboxylic acid(TCA)cycle,and the electron transport chain(etc),thereby enhancing mitochondrial efficiency and energy production.Mitochondrial NAD+biosynthesis involves multiple pathways,including the de novo synthesis from tryptophan via the kynurenine and the salvage pathway,which recycles nicotinamide back to NAD+.Moreover,NAD+concentrations influence mitochondrial dynamics such as fusion,fission,and mitophagy,which are essential for preserving mitochondrial integrity and function.NAD+alsomodulates the balance between glycolysis and oxidative phosphorylation,influencing the metabolic flexibility of cells.During NAD+depletion,mainly in metabolic disorders,cells often shift towards anaerobic glycolysis,reducing ATP production efficiency and increasing lactate production.This metabolic shift is associated with various pathophysiological conditions,including insulin resistance,neurodegeneration,and muscle wasting.This reviewexplores themultifaceted functions of NAD+in regulating mitochondrialmetabolism.It highlights the underlying causes and pathological outcomes of disrupted NAD+metabolism while exploring potential therapeutic targets and treatment strategies.展开更多
The Helicobacter pylori vacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has b...The Helicobacter pylori vacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has been reported to alter overall cellular metabolism, there is little known about the consequences of extended exposure to the toxin. Here, we describe studies to address this gap in knowledge, which have revealed that mitochondrial dysfunction and fragmentation are followed by a time-dependent recovery of mitochondrial structure, mitochondrial transmembrane potential, and cellular ATP levels. Cells exposed to VacA also initially demonstrated a reduction in oxidative phosphorylation, as well as increase in compensatory aerobic glycolysis. These metabolic alterations were reversed in cells with limited toxin exposure, congruent with the recovery of mitochondrial transmembrane potential and the absence of cytochrome c release from the mitochondria. Taken together, these results are consistent with a model that mitochondrial structure and function are restored in VacA-intoxicated cells.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
Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynth...Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynthesis of reactive oxygen species,the control of calcium homeostasis,and the triggering of cell death.The disruption of anyone of these processes has been shown to impact strongly the function of all cells,but especially of neurons.In this review,we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis,Parkinson's disease and Alzheimer's disease.We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle:fusion,fission,production of reactive oxygen species and energy failure.Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes.Therefore,in order to get in depth insights into their health status in neurodegenerative diseases,we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes.Current techniques include Mitostress,Mitotracker,transmission electron microscopy,oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health.We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction.These include canonical drugs,natural compounds,supplements,lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy.In conclusion,because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases,it is critical to develop novel methods to measure the mitochondrial state,and novel therapeutic strategies aimed at improving their health.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
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
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.
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.
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 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.
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 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 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.
基金supported by the National Science Foundation of China(Grant Nos.:U23A20516,82273897,and 82141203)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine,China(Grant No.:2023YZZ02)+3 种基金Shanghai Municipal Health Commission's Traditional Chinese Medicine Research Project,China(Grant No.:2022CX005)the Shanghai Science and Technology Innovation Action Plans of the Shanghai Science and Technology Committee,China(Grant No.:21S21900600)the Three-year Action Plan of the Shanghai Traditional Chinese Medicine Development and Inheritance Program,China(Program No.:ZY(2021-2023)-0401)the Basic Scientific Research Project of Liaoning Province Education Department,China(Project No.:LJKZ0832).
文摘Inflammatory bowel disease(IBD)is a chronic and recurrent intestinal disease,and has become a major global health issue.Individuals with IBD face an elevated risk of developing colorectal cancer(CRC),and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC.This review covers the pathogenesis of IBD and CRC,focusing on mitochondrial dysfunction,and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function.Additionally,recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC,encompassing mitochondrial damage,release of mitochondrial DNA(mtDNA),and impairment of mitophagy,are thoroughly summarized.The review also provides a systematic overview of natural compounds(such as flavonoids,alkaloids,and diterpenoids),Chinese medicines,and intestinal microbiota,which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function.In the future,it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function,which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.
基金A fellowship support from the Golda Meir Fellowship Fund,The Hebrew University of Jerusalem,Israel。
文摘Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential for mitochondrial metabolism,functioning both as redox coenzymes and as signaling agents that help regulate cellular balance.Thus,while its major role is in energy production,NAD+is widely recognized as a metabolic cofactor and also serves as a substrate for various enzymes involved in cellular signaling,like sirtuins(SIRTs),poly(ADP-ribosyl)polymerases(PARPs),mono(ADP-ribosyl)transferases,and CD38.Sirtuins,a family of NAD+-dependent deacetylases,are critical in this regulatory network.SIRT3 removes acetyl groups from and enhances the activity of key enzymes that participate in fatty acid breakdown,the tricarboxylic acid(TCA)cycle,and the electron transport chain(etc),thereby enhancing mitochondrial efficiency and energy production.Mitochondrial NAD+biosynthesis involves multiple pathways,including the de novo synthesis from tryptophan via the kynurenine and the salvage pathway,which recycles nicotinamide back to NAD+.Moreover,NAD+concentrations influence mitochondrial dynamics such as fusion,fission,and mitophagy,which are essential for preserving mitochondrial integrity and function.NAD+alsomodulates the balance between glycolysis and oxidative phosphorylation,influencing the metabolic flexibility of cells.During NAD+depletion,mainly in metabolic disorders,cells often shift towards anaerobic glycolysis,reducing ATP production efficiency and increasing lactate production.This metabolic shift is associated with various pathophysiological conditions,including insulin resistance,neurodegeneration,and muscle wasting.This reviewexplores themultifaceted functions of NAD+in regulating mitochondrialmetabolism.It highlights the underlying causes and pathological outcomes of disrupted NAD+metabolism while exploring potential therapeutic targets and treatment strategies.
文摘The Helicobacter pylori vacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has been reported to alter overall cellular metabolism, there is little known about the consequences of extended exposure to the toxin. Here, we describe studies to address this gap in knowledge, which have revealed that mitochondrial dysfunction and fragmentation are followed by a time-dependent recovery of mitochondrial structure, mitochondrial transmembrane potential, and cellular ATP levels. Cells exposed to VacA also initially demonstrated a reduction in oxidative phosphorylation, as well as increase in compensatory aerobic glycolysis. These metabolic alterations were reversed in cells with limited toxin exposure, congruent with the recovery of mitochondrial transmembrane potential and the absence of cytochrome c release from the mitochondria. Taken together, these results are consistent with a model that mitochondrial structure and function are restored in VacA-intoxicated cells.
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.
文摘Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynthesis of reactive oxygen species,the control of calcium homeostasis,and the triggering of cell death.The disruption of anyone of these processes has been shown to impact strongly the function of all cells,but especially of neurons.In this review,we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis,Parkinson's disease and Alzheimer's disease.We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle:fusion,fission,production of reactive oxygen species and energy failure.Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes.Therefore,in order to get in depth insights into their health status in neurodegenerative diseases,we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes.Current techniques include Mitostress,Mitotracker,transmission electron microscopy,oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health.We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction.These include canonical drugs,natural compounds,supplements,lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy.In conclusion,because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases,it is critical to develop novel methods to measure the mitochondrial state,and novel therapeutic strategies aimed at improving their health.
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 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.
