The roles of mitochondria in global and local intracellular calcium signalling

Nature Reviews Molecular Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

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Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease

Physiology, Journal Year: 2024, Volume and Issue: 39(5), P. 247 - 268

Published: May 7, 2024

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the uniporter rapidly enhances NADH ATP production. However, maintaining homeostasis critical: insufficient impairs stress adaptation, overload can trigger cell death. this review, we delve into recent insights further defining relationship between dynamics oxidative phosphorylation. Our focus on how such regulation affects cardiac function disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, cardiomyopathies, Barth syndrome, Friedreich's ataxia. Several themes emerge from data. First, critical for fuel substrate selection, metabolite import, matching of supply to demand. Second, regulates both production response reactive oxygen species (ROS), balance its pro- antioxidant effects key it contributes pathological states. Third, exerts localized electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These hinge specific transporters, as or Na+/Ca2+ exchanger, may be noticeable acutely, contributing differently phenotypes depending whether transporters are acutely chronically modified. Perturbations these novel relationships during disease states either serve compensatory exacerbate impairments Consequently, targeting holds promise a therapeutic strategy variety diseases characterized contractile failure arrhythmias.

Language: Английский

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MCU genetically altered mice suggest how mitochondrial Ca2+ regulates metabolism

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(10), P. 918 - 928

Published: April 29, 2024

Language: Английский

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Early Synapse-Specific Alterations of Photoreceptor Mitochondria in the EAE Mouse Model of Multiple Sclerosis

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 206 - 206

Published: Jan. 30, 2025

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) linked to many neurological disabilities. The visual frequently impaired in MS. In previous studies, we observed early malfunctions rod photoreceptor ribbon synapses EAE mouse model MS that included alterations synaptic vesicle cycling and disturbances presynaptic Ca2+ homeostasis. Since these events are highly energy-demanding, analyzed whether mitochondria, which play a major role energy metabolism, might be involved at stage. Rod terminals contain single large mitochondrion next ribbon. present study, expression functionally relevant mitochondrial proteins (MIC60, ATP5B, COX1, PINK1, DRP1) by high-resolution qualitative quantitative immunofluorescence microscopy, immunogold electron microscopy Western blot experiments. We decreased mitochondria photoreceptors stage, suggesting dysfunctions important synapse pathology. Interestingly, were strongly compromised EAE, whereas extra-synaptic inner segments remained unchanged, demonstrating functional heterogeneity mitochondria.

Language: Английский

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Effects of aging on calcium channels in skeletal muscle

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: March 19, 2025

In skeletal muscle, calcium is not only essential to stimulate and sustain their contractions but also for muscle embryogenesis, regeneration, energy production in mitochondria, fusion. Different ion channels contribute achieving the various functions of muscles. Muscle contraction initiated by releasing from sarcoplasmic reticulum through ryanodine receptor gated mechanically four dihydropyridine receptors T-tubules. The influx store-operated sustains stimulates regeneration. Mitochondrial uniporter allows entry into mitochondria oxidative phosphorylation. Aging alters expression activity these different channels, resulting a reduction force generation regeneration capacity. Regular physical training bioactive molecules nutrients can prevent effects aging on channels. This review focuses current knowledge muscles’

Language: Английский

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Chimeric Cell Therapy Transfers Healthy Donor Mitochondria in Duchenne Muscular Dystrophy

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(7), P. 1819 - 1829

Published: July 17, 2024

Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by dystrophin gene mutations and mitochondrial dysfunction, leading to progressive muscle weakness premature death of DMD patients. We developed human Dystrophin Expressing Chimeric (DEC) cells, created the fusion myoblasts from normal donors patients, as foundation for DT-DEC01 therapy DMD. Our preclinical studies on mdx mouse models revealed enhanced expression functional improvements in cardiac, respiratory, skeletal muscles after systemic intraosseous DEC administration. The current study explored feasibility transfer within which crucial developing new therapeutic strategies Following staining with MitoTracker Deep Red Green dyes, was assessed Flow cytometry (FACS) confocal microscopy. PEG-mediated healthy (MB

Language: Английский

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Identification of VDAC1 as a mitochondria-related target of Duchenne muscular dystrophy based on bioinformatics analysis and in vitro experiments

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 158, P. 114836 - 114836

Published: May 12, 2025

Language: Английский

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