Mitochondria–membranous organelle contacts at a glance

Journal of Cell Science, Год журнала: 2025, Номер 138(9)

Опубликована: Май 1, 2025

ABSTRACT Mitochondrial contact sites are specialized interfaces where mitochondria physically interact with other organelles. Stabilized by molecular tethers and defined unique proteomic lipidomic profiles, these enable direct interorganellar communication functional coordination, playing crucial roles in cellular physiology homeostasis. Recent advances have expanded our knowledge of site-resident proteins, illuminated the dynamic adaptive nature interfaces, clarified their contribution to pathophysiology. In this Cell Science at a Glance article accompanying poster, we summarize mitochondrial contacts that been characterized mammals, mechanisms underlying formation, principal functions.

Язык: Английский

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Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing

Molecular Metabolism, Год журнала: 2024, Номер 88, С. 102003 - 102003

Опубликована: Авг. 6, 2024

Ageing is associated with mitochondrial dysfunction and increased oxidative stress. Exercise generates endogenous reactive oxygen species (ROS) promotes rapid remodelling. We investigated the role of Peroxiredoxin 2 (PRDX-2) in adaptations to exercise ageing using Caenorhabditis elegans as a model system. PRDX-2 was required for remodelling response mediated by DAF-16 transcription factor activation regulation fusion gene eat-3. Employing an acute recovery cycle, we demonstrated exercise-induced ER contact sites (MERCS) assembly dependent on signalling. There fragmentation, elevated ROS altered redox state concomitant impaired nuclear localisation during ageing. Similarly, prdx-2 mutant strain exhibited fragmentation failure activate fusion. Collectively, our data highlight critical orchestrating physiological stress regulating localisation.

Язык: Английский

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The suppressive effects of Crocin from Saffron on allergic airway inflammation through Drp1/Nfr1/Mfn2/Pgc1-alpha signaling pathway in mice

Journal of Ethnopharmacology, Год журнала: 2024, Номер 337, С. 118862 - 118862

Опубликована: Сен. 24, 2024

Язык: Английский

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Redox Regulation of Proteostasis

Journal of Biological Chemistry, Год журнала: 2024, Номер 300(12), С. 107977 - 107977

Опубликована: Ноя. 8, 2024

Язык: Английский

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Regulatory function of endoplasmic reticulum stress in colorectal cancer: Mechanism, facts, and perspectives

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114024 - 114024

Опубликована: Янв. 6, 2025

Язык: Английский

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A look at MERCs as UPR^mt regulatory hubs in age-associated heart diseases

The Journal of Cardiovascular Aging, Год журнала: 2025, Номер 5(1)

Опубликована: Янв. 22, 2025

With the increase in life expectancy globally, challenge of dealing with aging becomes more prominent. Aging is a risk factor for several diseases, including cardiovascular disease. Mitochondria, which have long been studied relation to aging, play crucial role maintaining cellular homeostasis. However, there limitation interorganellar communication as organisms age. The unfolded protein response mitochondria (UPRmt) activated during stress maintain mitochondrial homeostasis and prevent accumulation damaged mitochondria. This involves signaling from nucleus, leading transcriptional changes. In context heart, this review explores terms function morphology. It also discusses impact UPRmt on cardiac diseases such heart failure, acute myocardial infarction, dilated cardiomyopathy. highlights potential mitochondria-endoplasmic reticulum contact sites (MERCs) modulating aging. Finally, it provides an update molecules that induce activity, potentially benefiting

Язык: Английский

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Elevated levels of S100A8 and S100A9 exacerbate muscle mitochondrial fragmentation in sepsis-induced muscle atrophy

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Фев. 28, 2025

Sepsis-induced skeletal muscle atrophy is common in septic patients with the increases risk of mortality and associated myocellular mitochondrial dysfunction. Nevertheless, specific mechanism sepsis remains unclear. Here we conducted a clinical retrospective analysis observed elevation index (ΔSMI) was an independent factor for 60-day patients. Moreover, mouse model sepsis, also observed, which upregulation S100a8/a9-mediated Inhibition S100a8/a9 significantly improved function alleviated atrophy. Conversely, administration recombinant protein exacerbated energy exhaustion myocyte Mechanistically, binding to RAGE induced Drp1 phosphorylation fragmentation, resulting Additionally, ablation or inhibitor reduced Drp1-mediated fission, morphology function. Our findings indicated pivotal role driving fragmentation Targeting S100a8/a9-RAGE-initiated fission might offer promising therapeutic intervention against linked increased patients; this study, authors identify S100a8/a9-RAGE pathway as key driver

Язык: Английский

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Serine-129 phosphorylated α-synuclein drives mitochondrial dysfunction and calcium dysregulation in Parkinson’s disease model

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Март 31, 2025

Phosphorylation of α -synuclein at serine-129 (p- -syn) is a hallmark Parkinson’s disease (PD) and constitutes nearly 90% α-synuclein in Lewy bodies, playing critical role progression. Despite its pathological significance, the molecular targets mechanisms driving p- -syn-induced toxicity, particularly mitochondrial dysfunction, remain poorly understood. In this study, we observed dysfunction primary cortical neurons derived from mice overexpressing human (h- -syn), which also exhibit elevated levels -syn. Notably, inhibiting Ser129 phosphorylation improved function, underscoring -syn damage. To investigate mechanism, performed co-immunoprecipitation (CO-IP) combined with mass spectrometry (MS) to identify binding proteins. This analysis identified protein tyrosine phosphatase interacting 51 (PTPIP51) vesicle-associated membrane protein-associated B (VAPB) as key partners. Both proteins are localized mitochondria-associated endoplasmic reticulum mem-brane (MAM) essential for calcium transfer between (ER) mitochondria. Our results showed that binds PTPIP51 VAPB, disrupting signaling ER Importantly, inhibition partially rescued homeostasis. These findings uncover novel mechanism by drives dysregulation through interactions MAM-associated proteins, providing new insights into PD pathogenesis potential therapeutic targets.

Язык: Английский

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The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Abstract Kidney diseases are among the fastest worldwide growing pathologies. This growth together with their high mortality rate emphasizes importance of generating vital information about mechanism involved in pathophysiology to determine possible therapeutic targets. Recently, mitochondrial damage and implication reactive oxygen spices (ROS) signaling redox homeostasis have emerged as a hub point pathologic renal ROS low levels necessary maintain cell processes well mitochondria its association other organelles, especially endoplasmic reticulum (ER). However, how interacts interferes cellular has not been fully integrated. Furthermore, higher concentrations, these promotes pathways linked disease progression like, biogenesis reduction, ER stress, calcium overload, inflammation, death fibrosis. Therefore, aim this review is describe molecular mechanisms influence on homeostasis, focusing lipid metabolism ß-oxidation, biogenesis, inflammations, stress effects alteration genesis development disease, emphasis acute kidney injury (AKI) chronic (CKD).

Язык: Английский

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Premature skeletal muscle aging in VPS13A deficiency relates to impaired autophagy

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Апрель 24, 2025

VPS13A disease (chorea-acanthocytosis), is an ultra-rare autosomal recessive neurodegenerative disorder caused by mutations of the gene encoding Vps13A. Increased serum levels muscle isoform creatine kinase associated with often asymptomatic pathology are among poorly understood early clinical manifestations disease. Here, we carried out integrated analysis skeletal from Vps13a-/- mice and patient biopsies. The absence Vps13A impaired autophagy, resulting in pathologic metabolic remodeling characterized cellular energy depletion, increased protein/lipid oxidation a hyperactivated unfolded protein response. This was defects myofibril stability myofibrillar regulatory proteome, accumulation myocyte senescence marker, NCAM1. In mice, impairment autophagy further supported lacking effect starvation alone or combination colchicine on markers. As proof concept, showed that rapamycin treatment rescued terminal phase markers LAMP1 p62 as well NCAM1, supporting connection between accelerated aging VPS13A. premature also corroborated local activation pro-inflammatory NF-kB-related pathways both patients Our data link for first time inflammaging dysfunction biological relevance our mouse findings, human biopsy data, shed new light role homeostasis.

Язык: Английский

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