RRC ID 56220
Author Scholtes C, Bellemin S, Martin E, Carre-Pierrat M, Mollereau B, Gieseler K, Walter L.
Title DRP-1-mediated apoptosis induces muscle degeneration in dystrophin mutants.
Journal Sci Rep
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.
Volume 8(1)
Pages 7354
Published 2018-5-9
DOI 10.1038/s41598-018-25727-8
PII 10.1038/s41598-018-25727-8
PMID 29743663
PMC PMC5943356
MeSH Animals Apoptosis / genetics* Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism* Caspases / metabolism Dynamins / metabolism* Dystrophin / genetics* Locomotion / genetics Mitochondria / metabolism Mitochondrial Dynamics Muscles / metabolism* Mutation*
IF 4.011
Times Cited 7
C.elegans tm1108