DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants

Abstract Mitochondria are double-membrane subcellular organelles with highly conserved metabolic functions including ATP production. Mitochondria shapes change continually through the combined actions of fission and fusion events rendering mitochondrial network very dynamic. Mitochondria are largely...

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Autores principales:	Charlotte Scholtes, Stéphanie Bellemin, Edwige Martin, Maïté Carre-Pierrat, Bertrand Mollereau, Kathrin Gieseler, Ludivine Walter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/598aa1b7996040d6963ba68839b2d8b9
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spelling	oai:doaj.org-article:598aa1b7996040d6963ba68839b2d8b92021-12-02T12:32:22ZDRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants10.1038/s41598-018-25727-82045-2322https://doaj.org/article/598aa1b7996040d6963ba68839b2d8b92018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25727-8https://doaj.org/toc/2045-2322Abstract Mitochondria are double-membrane subcellular organelles with highly conserved metabolic functions including ATP production. Mitochondria shapes change continually through the combined actions of fission and fusion events rendering mitochondrial network very dynamic. Mitochondria are largely implicated in pathologies and mitochondrial dynamics is often disrupted upon muscle degeneration in various models. Currently, the exact roles of mitochondria in the molecular mechanisms that lead to muscle degeneration remain poorly understood. Here we report a role for DRP-1 in regulating apoptosis induced by dystrophin-dependent muscle degeneration. We found that: (i) dystrophin-dependent muscle degeneration was accompanied by a drastic increase in mitochondrial fragmentation that can be rescued by genetic manipulations of mitochondrial dynamics (ii) the loss of function of the fission gene drp-1 or the overexpression of the fusion genes eat-3 and fzo-1 provoked a reduction of muscle degeneration and an improved mobility of dystrophin mutant worms (iii) the functions of DRP-1 in apoptosis and of others apoptosis executors are important for dystrophin-dependent muscle cell death (iv) DRP-1-mediated apoptosis is also likely to induce age-dependent loss of muscle cell. Collectively, our findings point toward a mechanism involving mitochondrial dynamics to respond to trigger(s) of muscle degeneration via apoptosis in Caenorhabditis elegans.Charlotte ScholtesStéphanie BelleminEdwige MartinMaïté Carre-PierratBertrand MollereauKathrin GieselerLudivine WalterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charlotte Scholtes Stéphanie Bellemin Edwige Martin Maïté Carre-Pierrat Bertrand Mollereau Kathrin Gieseler Ludivine Walter DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
description	Abstract Mitochondria are double-membrane subcellular organelles with highly conserved metabolic functions including ATP production. Mitochondria shapes change continually through the combined actions of fission and fusion events rendering mitochondrial network very dynamic. Mitochondria are largely implicated in pathologies and mitochondrial dynamics is often disrupted upon muscle degeneration in various models. Currently, the exact roles of mitochondria in the molecular mechanisms that lead to muscle degeneration remain poorly understood. Here we report a role for DRP-1 in regulating apoptosis induced by dystrophin-dependent muscle degeneration. We found that: (i) dystrophin-dependent muscle degeneration was accompanied by a drastic increase in mitochondrial fragmentation that can be rescued by genetic manipulations of mitochondrial dynamics (ii) the loss of function of the fission gene drp-1 or the overexpression of the fusion genes eat-3 and fzo-1 provoked a reduction of muscle degeneration and an improved mobility of dystrophin mutant worms (iii) the functions of DRP-1 in apoptosis and of others apoptosis executors are important for dystrophin-dependent muscle cell death (iv) DRP-1-mediated apoptosis is also likely to induce age-dependent loss of muscle cell. Collectively, our findings point toward a mechanism involving mitochondrial dynamics to respond to trigger(s) of muscle degeneration via apoptosis in Caenorhabditis elegans.
format	article
author	Charlotte Scholtes Stéphanie Bellemin Edwige Martin Maïté Carre-Pierrat Bertrand Mollereau Kathrin Gieseler Ludivine Walter
author_facet	Charlotte Scholtes Stéphanie Bellemin Edwige Martin Maïté Carre-Pierrat Bertrand Mollereau Kathrin Gieseler Ludivine Walter
author_sort	Charlotte Scholtes
title	DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
title_short	DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
title_full	DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
title_fullStr	DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
title_full_unstemmed	DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
title_sort	drp-1-mediated apoptosis induces muscle degeneration in dystrophin mutants
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/598aa1b7996040d6963ba68839b2d8b9
work_keys_str_mv	AT charlottescholtes drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT stephaniebellemin drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT edwigemartin drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT maitecarrepierrat drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT bertrandmollereau drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT kathringieseler drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants AT ludivinewalter drp1mediatedapoptosisinducesmuscledegenerationindystrophinmutants
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DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants

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