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Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling
Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presen...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003250/ https://www.ncbi.nlm.nih.gov/pubmed/24751540 http://dx.doi.org/10.1083/jcb.201312066 |
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author | Eisner, Verónica Lenaers, Guy Hajnóczky, György |
author_facet | Eisner, Verónica Lenaers, Guy Hajnóczky, György |
author_sort | Eisner, Verónica |
collection | PubMed |
description | Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presented by skeletal muscle, where mostly globular-shaped mitochondria are densely packed into the narrow intermyofilamental space, limiting the interorganellar interactions. We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation–contraction coupling, providing a potential pathomechanism contributing to myopathies. |
format | Online Article Text |
id | pubmed-4003250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40032502014-10-28 Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling Eisner, Verónica Lenaers, Guy Hajnóczky, György J Cell Biol Research Articles Genetic targeting experiments indicate a fundamental role for mitochondrial fusion proteins in mammalian physiology. However, owing to the multiple functions of fusion proteins, their related phenotypes are not necessarily caused by altered mitochondrial fusion. Perhaps the biggest mystery is presented by skeletal muscle, where mostly globular-shaped mitochondria are densely packed into the narrow intermyofilamental space, limiting the interorganellar interactions. We show here that mitochondria form local networks and regularly undergo fusion events to share matrix content in skeletal muscle fibers. However, fusion events are less frequent and more stable in the fibers than in nondifferentiated myoblasts. Complementation among muscle mitochondria was suppressed by both in vivo genetic perturbations and chronic alcohol consumption that cause myopathy. An Mfn1-dependent pathway is revealed whereby fusion inhibition weakens the metabolic reserve of mitochondria to cause dysregulation of calcium oscillations during prolonged stimulation. Thus, fusion dynamically connects skeletal muscle mitochondria and its prolonged loss jeopardizes bioenergetics and excitation–contraction coupling, providing a potential pathomechanism contributing to myopathies. The Rockefeller University Press 2014-04-28 /pmc/articles/PMC4003250/ /pubmed/24751540 http://dx.doi.org/10.1083/jcb.201312066 Text en © 2014 Eisner et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Eisner, Verónica Lenaers, Guy Hajnóczky, György Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title | Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title_full | Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title_fullStr | Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title_full_unstemmed | Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title_short | Mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
title_sort | mitochondrial fusion is frequent in skeletal muscle and supports excitation–contraction coupling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003250/ https://www.ncbi.nlm.nih.gov/pubmed/24751540 http://dx.doi.org/10.1083/jcb.201312066 |
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