Mitophagy in human health, ageing and disease

Nature Metabolism, Год журнала: 2023, Номер 5(12), С. 2047 - 2061

Опубликована: Ноя. 30, 2023

Язык: Английский

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Mitochondrial quality control in human health and disease

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Май 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Язык: Английский

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SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(4)

Опубликована: Апрель 1, 2024

Abstract Introduction Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays role in the development PDN, but its pathogenesis and mechanism not been fully investigated. Methods In this study, we used high‐fat diet/low‐dose streptozotocin‐induced rats as model type 2 diabetes mellitus. Behavioral testing, whole‐cell patch‐clamp recordings dorsal root ganglion (DRG) neurons, complex sensory nerve conduction velocity were to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, transmission electron microscopy evaluate function morphology mitochondria DRG. Real‐time PCR, western blot, immunofluorescence performed investigate mechanism. Results We found damaged accumulated mitophagy was inhibited PDN rats. The expression sirtuin 3 (SIRT3), which an NAD + ‐dependent deacetylase mitochondria, inhibited. Overexpression SIRT3 DRG neurons by intrathecally administered LV‐SIRT3 lentivirus ameliorated neurological dysfunctions. This evidenced reversal allodynia nociceptor hyperexcitability, well restoration MMP ATP levels. restored activating FoxO3a‐PINK1‐Parkin signaling pathway. effects overexpression, including improvement impaired mitophagy, PINK1 Parkin expression, counteracted when FoxO3a siRNA injected. Conclusion These results showed overexpression ameliorates via activation FoxO3a‐PINK1‐Parkin‐mediated suggesting may become encouraging therapeutic strategy for PDN.

Язык: Английский

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Acidic Nanoparticles Restore Lysosomal Acidification and Rescue Metabolic Dysfunction in Pancreatic β-Cells under Lipotoxic Conditions

ACS Nano, Год журнала: 2024, Номер 18(24), С. 15452 - 15467

Опубликована: Июнь 3, 2024

Type 2 diabetes (T2D), a prevalent metabolic disorder lacking effective treatments, is associated with lysosomal acidification dysfunction, as well autophagic and mitochondrial impairments. Here, we report series of biodegradable poly(butylene tetrafluorosuccinate-co-succinate) polyesters, comprising 1,4-butanediol linker varying ratios tetrafluorosuccinic acid (TFSA) succinic components, to engineer lysosome-acidifying nanoparticles (NPs). The synthesized NPs are spherical diameters ≈100 nm have low polydispersity good stability. Notably, TFSA NPs, which composed entirely TFSA, exhibit the strongest degradation capability superior acidifying properties. We further reveal significant downregulation vacuolar (H+)-ATPase subunits, responsible for maintaining acidification, in human T2D pancreatic islets, INS-1 β-cells under chronic lipotoxic conditions, tissues high-fat-diet (HFD) mice. Treatment restores function, activity, thereby improving function cells HFD mice lipid overload. Importantly, administration reduces insulin resistance improves glucose clearance. These findings highlight therapeutic potential T2D.

Язык: Английский

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Natural products as pharmacological modulators of mitochondrial dysfunctions for the treatment of diabetes and its complications: An update since 2010

Pharmacological Research, Год журнала: 2024, Номер 200, С. 107054 - 107054

Опубликована: Янв. 4, 2024

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose substantial and escalating health healthcare challenge on global scale. Current strategies addressing diabetes are mainly symptomatic there fewer available curative pharmaceuticals for diabetic complications. Thus, is an urgent need to identify novel pharmacological targets agents. The impaired mitochondria have been the etiology of complications, intervention mitochondrial dysfunction represents attractive breakthrough point treatments Natural products (NPs), multicenter characteristics, multi-pharmacological activities lower toxicity, caught attentions modulators functions in therapeutical filed This review summarizes recent progresses potential 39 NPs 2 plant-extracted mixtures improve against It expected that this work may be useful accelerate development innovative drugs originated from upcoming therapeutics

Язык: Английский

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Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia–reperfusion by triggering the release of mitochondrial DNA

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Авг. 3, 2023

The cause of aggravation diabetic myocardial damage is yet to be elucidated; mitochondrial function has been a longstanding focus research. During ischaemia-reperfusion (MI/R), it remains unclear whether reduced fusion exacerbates injury by generating free damaged DNA (mitoDNA) and activating the cGAS-STING pathway.In this study, mouse model diabetes was established (by feeding mice high-fat diet (HFD) plus low dose streptozotocin (STZ)), MI/R cardiac ischaemia for 2 h reperfusion 30 min, cellular glycolipid toxicity induced high glucose (HG) palmitic acid (PA) in H9C2 cells.We observed that altered dynamics during led increased mitoDNA cytosol, activation pathway, phosphorylation downstream targets TBK1 IRF3. In we found cytosolic result HG PA, which also resulted signalling targets. Moreover, inhibition STING H-151 significantly ameliorated MFN2 knockdown both cell models. use fat-soluble antioxidant CoQ10 improved models.Our study elucidated critical role activation, triggered due decreased fusion, pathogenesis injury. This provides preclinical insights treatment Video Abstract.

Язык: Английский

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Mitochondrial Dynamics and Insulin Secretion

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13782 - 13782

Опубликована: Сен. 7, 2023

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as fission fusion, necessary to maintain shape function. Disturbances dynamics lead dysfunctional mitochondria, which contribute development progression numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence has been put forward that play a significant role metabolism-secretion coupling pancreatic β cells. The disruption is linked defects production increased apoptosis, ultimately impairing insulin secretion cell death. This review provides an overview molecular mechanisms controlling dynamics, their dysfunction cells, pharmaceutical agents targeting proteins, division inhibitor-1 (mdivi-1), dynasore, P110, 15-oxospiramilactone (S3).

Язык: Английский

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The role of Mitofusin-1 and Mitofusin-2 in periodontal disease: a comprehensive review

Frontiers in Oral Health, Год журнала: 2025, Номер 6

Опубликована: Янв. 17, 2025

Periodontal disease is a widespread chronic inflammatory state influencing the supporting anatomy of teeth, distinguished by oxidative stress, progressive bone loss, and tissue damage. Recent articles have highlighted significance mitochondrial dynamics, mainly Mitofusin-1 (MFN1) along with Mitofusin-2 (MFN2), inflammation regulation, homeostasis, in cellular function. The aim current study to comprehensively review including evaluate roles MFN2 MFN1 pathogenesis as well progression periodontal disease, foregrounding their effect on integrity, pathways, stress. Studies were selected depending inclusion criteria based health. Data from chosen vivo, clinical studies, vitro synthesized. Outcomes indicate that are important for preserving function, mitigating damage, fusion. Decreased levels these proteins related elevated inflammation, increased dysfunction tissues. comprehensive shows cell survival, dynamics within disease. prospective targeting therapeutic policy promising, presenting avenues upgraded management regeneration.

Язык: Английский

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The protection of nicotinamide riboside against diabetes mellitus-induced bone loss via OXPHOS

Bone, Год журнала: 2025, Номер unknown, С. 117411 - 117411

Опубликована: Янв. 1, 2025

Язык: Английский

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Evaluating the Molecular Interactions between Type 2 Diabetes Mellitus and Parkinson’s Disease: Role of Antidiabetic Drugs as Promising Therapeutics

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Evidence from previous research demonstrates a relationship between diabetes mellitus (DM) and Parkinson's disease (PD). T2DM is associated with chronic glucose dysregulation, as an etiological factor. It inhibits neuronal function through disrupted insulin signaling oxidative stress, which ultimately lead to the loss of dopaminergic neurons in substantia nigra (SN). Interactions PD were analyzed by gene expression, coexpression, set enrichment via NCBI STRING databases following pathways like KEGG Reactome. The study identified nine key interactions published literature on different search engines that are involved progression these diseases. Furthermore, some genetic nongenetic risk factors, mutations environmental also PD. This review highlights limitations currently available drug treatments for diseases examines modern therapeutic approaches address neurodegenerative metabolic abnormalities. We critically assess current experimental methodologies aimed at unraveling pathophysiological mechanisms linking while addressing challenges impeding comprehensive understanding concurrent emergence debilitating age-related conditions.

Язык: Английский

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