Mitochondrial dysfunction causes Ca2+ overload and ECM degradation-mediated muscle damage in C. elegans
dc.contributor.author | Sudevan, S | |
dc.contributor.author | Takiura, M | |
dc.contributor.author | Kubota, Y | |
dc.contributor.author | Higashitani, N | |
dc.contributor.author | Cooke, M | |
dc.contributor.author | Ellwood, RA | |
dc.contributor.author | Etheridge, T | |
dc.contributor.author | Szewczyk, NJ | |
dc.contributor.author | Higashitani, A | |
dc.date.accessioned | 2020-01-17T15:19:29Z | |
dc.date.issued | 2019-06-04 | |
dc.description.abstract | Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)-based proteolysis and, consequentially, muscle cell dystrophy. We found that inhibition of the mitochondrial electron transport chain causes paralysis as well as muscle structural damage in the nematode Caenorhabditis elegans. This was associated with a significant decline in collagen content. Both paralysis and muscle damage could be rescued with collagen IV overexpression, matrix metalloproteinase (MMP), and Furin inhibitors in Antimycin A-treated animal as well as in the C. elegans Duchenne muscular dystrophy model. Additionally, muscle cytosolic calcium increased in the Antimycin A-treated worms, and its down-regulation rescued the muscle damage, suggesting that calcium overload acts as one of the early triggers and activates Furin and MMPs for collagen degradation. In conclusion, we have established ECM degradation as an important pathway of muscle damage.-Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., Etheridge, T., Szewczyk, N. J., Higashitani, A. Mitochondrial dysfunction causes Ca2+ overload and ECM degradation-mediated muscle damage in C. elegans. | en_GB |
dc.description.sponsorship | Ministry of Education, Culture, Sports, Science, and Technology (MEXT) | en_GB |
dc.description.sponsorship | Cross-Ministerial Strategic Innovation Promotion Program | en_GB |
dc.description.sponsorship | Advanced Research and Development Programs for Medical Innovation (AMED-CREST | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | UK Space Agency | en_GB |
dc.description.sponsorship | Science and Technology Facilities Council (STFC) | en_GB |
dc.description.sponsorship | Otsuka Toshimi Foundation | en_GB |
dc.description.sponsorship | Tohoku University | en_GB |
dc.description.sponsorship | Japan Student Services Organization | en_GB |
dc.identifier.citation | Vol. 33 (8), pp. 9540 - 9550 | en_GB |
dc.identifier.doi | 10.1096/fj.201802298R | |
dc.identifier.grantnumber | 15H05937 | en_GB |
dc.identifier.grantnumber | 15K21745 | en_GB |
dc.identifier.grantnumber | 14537491 | en_GB |
dc.identifier.grantnumber | 16814305 | en_GB |
dc.identifier.grantnumber | BB/N015894/1 | en_GB |
dc.identifier.grantnumber | BB/P025781/1 | en_GB |
dc.identifier.grantnumber | ST/R005737/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/40478 | |
dc.language.iso | en | en_GB |
dc.publisher | Federation of American Society of Experimental Biology (FASEB) | en_GB |
dc.rights | © 2019 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | Antimycin A | en_GB |
dc.subject | collagen | en_GB |
dc.subject | Furin | en_GB |
dc.subject | DMD | en_GB |
dc.subject | MMP | en_GB |
dc.title | Mitochondrial dysfunction causes Ca2+ overload and ECM degradation-mediated muscle damage in C. elegans | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-01-17T15:19:29Z | |
dc.description | This is the final version. Available on open access from the Federation of American Society of Experimental Biology via the DOI in this record | en_GB |
dc.identifier.eissn | 1530-6860 | |
dc.identifier.journal | FASEB Journal | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-04-29 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-06-04 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-01-17T14:32:49Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-01-17T15:19:33Z | |
refterms.panel | C | en_GB |
refterms.depositException | publishedGoldOA |
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Except where otherwise noted, this item's licence is described as © 2019 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.