Mitochondrial complex I activity in microglia sustains neuroinflammation

Nature, Год журнала: 2024, Номер 628(8006), С. 195 - 203

Опубликована: Март 13, 2024

Abstract Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark several chronic neurological diseases, including multiple sclerosis 1 . Distinct metabolic and mitochondrial features guide the activation diverse functional states 2 However, how these act to perpetuate inflammation central nervous system unclear. Here, using multiomics approach, we identify molecular signature that sustains microglia through complex I activity driving reverse electron transport production reactive oxygen species. Mechanistically, blocking in pro-inflammatory protects against neurotoxic damage improves outcomes an animal disease model vivo. Complex potential therapeutic target foster neuroprotection inflammatory disorders 3

Язык: Английский

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Mitochondrial diseases: from molecular mechanisms to therapeutic advances

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 9, 2025

Abstract Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism signaling. They possess various metabolic quality control mechanisms crucial maintaining normal activities. Mitochondrial genetic disorders can arise from a wide range mutations in either mitochondrial or nuclear DNA, which encode proteins other contents. These defects lead to breakdown metabolism, such the collapse oxidative phosphorylation, one mitochondria’s most critical functions. diseases, common group disorders, characterized by significant phenotypic heterogeneity. Clinical symptoms manifest systems organs throughout body, with differing degrees forms severity. The complexity relationship between mitochondria diseases results an inadequate understanding genotype-phenotype correlation these historically making diagnosis treatment challenging often leading unsatisfactory clinical outcomes. However, recent advancements research technology have significantly improved our management conditions. translations mitochondria-related therapies actively progressing. This review focuses on physiological mitochondria, pathogenesis potential diagnostic therapeutic applications. Additionally, this discusses future perspectives diseases.

Язык: Английский

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MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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Mitochondrial dysfunction in drug-induced hepatic steatosis: recent findings and current concept

Clinics and Research in Hepatology and Gastroenterology, Год журнала: 2025, Номер 49(3), С. 102529 - 102529

Опубликована: Янв. 9, 2025

Язык: Английский

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Recent development of mitochondrial metabolism and dysfunction in osteoarthritis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 13, 2025

Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, extracellular matrix degradation. Disruptions dynamics, including impaired biogenesis, mitophagy, metabolic shifts from phosphorylation glycolysis, exacerbate damage promoting the production of reactive oxygen species matrix-degrading enzymes such ADAMTS MMPs. This review explores molecular mechanisms underlying OA, emphasizing its role homeostasis inflammation. Furthermore, it highlights emerging therapeutic strategies targeting pathways, antioxidants, mitophagy enhancers, modulators, potential interventions mitigate disease progression, which offer promising avenues for advancing personalized disease-modifying treatments OA.

Язык: Английский

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Post-traumatic stress disorder, diabetes mellitus, and alpha-lipoic acid

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Год журнала: 2025, Номер 21(1), С. 82 - 94

Опубликована: Фев. 23, 2025

Post-traumatic stress disorder (PTSD) is a prognostic factor for the development of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), increases risk cardiometabolic pathologies and neurodegenerative diseases. At same time, T2DM MetS can also cause major neurosis-like psychiatric symptoms characteristic PTSD. Their influence manifested through negative effects on central nervous system, in particular Oxidative chronic low-grade inflammation play an important role pathophysiology PTSD, MetS, T2DM, making them main therapeutic targets. Targeted oxidative stress, mitochondrial metabolism disorders, use antioxidants, α-lipoic acid (ALA), positively affect not only course comorbidities but manifestations In vitro vivo studies have demonstrated that ALA modulates number pathways associated with stress. addition, results clinical trials confirm antioxidant mechanism action patients obesity, 1 2. The neuroprotective activity being actively studied proving promising as approach treatment PTSD Despite significant potential ALA, its application limited by several barriers. particular, lack standardized protocols, well detailed assessment effectiveness alone. pharmacokinetic profile remains limited, which one factors hinder use. this context, there are certain prospects transportation systems based nanoparticles, potentially solve these problems. technologies so­lid lipid nanoparticles such niosomes, liposomes, nanostructured carriers micelles provide possibility local or systemic ALA. However, further preclinical needed to definitively determine feasibility search was conducted Scopus, Science Direct (from Elsevier) PubMed, including MEDLINE databases. keywords used were “α-lipoic acid”, “post-traumatic disorder”, “diabetes mellitus”, “metabolic syndrome”. A manual bibliography publications identify study could be found during online search.

Язык: Английский

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Resilience to diabetic retinopathy

Progress in Retinal and Eye Research, Год журнала: 2024, Номер 101, С. 101271 - 101271

Опубликована: Май 11, 2024

Chronic elevation of blood glucose at first causes relatively minor changes to the neural and vascular components retina. As duration hyperglycemia persists, nature extent damage increases becomes readily detectable. While this second, overt manifestation diabetic retinopathy (DR) has been studied extensively, what prevents maximal from very start remains largely unexplored. Recent studies indicate that diabetes (DM) engages mitochondria-based defense during retinopathy-resistant phase, thereby enables retina remain healthy in face hyperglycemia. Such resilience is transient, its deterioration results progressive accumulation retinal damage. The concepts co-emerge with these discoveries set stage for novel intellectual therapeutic opportunities within DR field. Identification biomarkers mediators protection DM-mediated will enable development resilience-based therapies indefinitely delay onset DR.

Язык: Английский

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Ceramides and mitochondrial homeostasis

Cellular Signalling, Год журнала: 2024, Номер 117, С. 111099 - 111099

Опубликована: Фев. 13, 2024

Язык: Английский

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Implication of Rac1 GTPase in molecular and cellular mitochondrial functions

Life Sciences, Год журнала: 2024, Номер 342, С. 122510 - 122510

Опубликована: Фев. 20, 2024

Rac1 is a member of the Rho GTPase family which plays major roles in cell mobility, polarity and migration, as fundamental regulator actin cytoskeleton. Signal transduction by occurs through interaction with multiple effector proteins, its activity regulated guanine nucleotide exchange factors (GEFs) GTPase-activating proteins (GAPs). The small protein mainly anchored to inner side plasma membrane but it can be found endocellular compartments, notably endosomes nuclei. localizes also into mitochondria where contributes regulation mitochondrial dynamics, including both mitobiogenesis mitophagy, addition signaling processes via different partners, such proapoptotic Bcl-2 chaperone sigma-1 receptor (σ-1R). form (mtRac1) has been understudied thus far, essential nuclear or forms, implication oxidative stress DNA damages. subject diverse post-translational modifications, geranylgeranylation importantly import anchorage membranes. In addition, translocation other p53. localization functions are discussed here, context human diseases cancers. Inhibitors have identified (NSC-23766, EHT-1864) some being developed for treatment cancer (MBQ-167) central nervous system (JK-50561). Their effects on mtRac1 warrant further investigations. An overview provided here.

Язык: Английский

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Overnutrition and Lipotoxicity: Impaired Efferocytosis and Chronic Inflammation as Precursors to Multifaceted Disease Pathogenesis

Biology, Год журнала: 2024, Номер 13(4), С. 241 - 241

Опубликована: Апрель 6, 2024

Overnutrition, driven by the consumption of high-fat, high-sugar diets, has reached epidemic proportions and poses a significant global health challenge. Prolonged overnutrition leads to deposition excessive lipids in adipose non-adipose tissues, condition known as lipotoxicity. The intricate interplay between overnutrition-induced lipotoxicity immune system plays pivotal role pathogenesis various diseases. This review aims elucidate consequences impaired efferocytosis, caused lipotoxicity-poisoned macrophages, leading chronic inflammation subsequent development severe infectious diseases, autoimmunity, cancer, well pulmonary cardiovascular Chronic promotes tissue expansion which induces cellular stress inflammatory responses, contributing insulin resistance, dyslipidemia, metabolic syndrome. Moreover, sustained exposure impairs efferocytic capacity compromising their ability efficiently engulf remove dead cells. unresolved perpetuates pro-inflammatory microenvironment, exacerbating damage promoting interaction overnutrition, lipotoxicity, efferocytosis highlights critical pathway through emerges, facilitating Understanding these connections sheds light on potential therapeutic avenues mitigate detrimental effects function homeostasis, thereby paving way for novel interventions aimed at reducing burden multifaceted diseases health.

Язык: Английский

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