{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:15:30Z","timestamp":1790813730723,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2014-04668"],"award-info":[{"award-number":["RGPIN-2014-04668"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-93760"],"award-info":[{"award-number":["MOP-93760"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOV-409262"],"award-info":[{"award-number":["MOV-409262"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","award":["FRQS-35184"],"award-info":[{"award-number":["FRQS-35184"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sepsis elicits skeletal muscle weakness and fiber atrophy. The accumulation of injured mitochondria and depressed mitochondrial functions are considered as important triggers of sepsis-induced muscle atrophy. It is unclear whether mitochondrial dysfunctions in septic muscles are due to the inadequate activation of quality control processes. We hypothesized that overexpressing Parkin, a protein responsible for the recycling of dysfunctional mitochondria by the autophagy pathway (mitophagy), would confer protection against sepsis-induced muscle atrophy by improving mitochondrial quality and content. Parkin was overexpressed for four weeks in the limb muscles of four-week old mice using intramuscular injections of adeno-associated viruses (AAVs). The cecal ligation and perforation (CLP) procedure was used to induce sepsis. Sham operated animals were used as controls. All animals were studied for 48 h post CLP. Sepsis resulted in major body weight loss and myofiber atrophy. Parkin overexpression prevented myofiber atrophy in CLP mice. Quantitative two-dimensional transmission electron microscopy revealed that sepsis is associated with the accumulation of enlarged and complex mitochondria, an effect which was attenuated by Parkin overexpression. Parkin overexpression also prevented a sepsis-induced decrease in the content of mitochondrial subunits of NADH dehydrogenase and cytochrome C oxidase. We conclude that Parkin overexpression prevents sepsis-induced skeletal muscle atrophy, likely by improving mitochondrial quality and contents.<\/jats:p>","DOI":"10.3390\/cells9061454","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T12:16:57Z","timestamp":1592223417000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Parkin Overexpression Attenuates Sepsis-Induced Muscle Wasting"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-5445","authenticated-orcid":false,"given":"Jean-Philippe","family":"Leduc-Gaudet","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre; Department of Critical Care, McGill University Health Centre, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"D\u00e9partement des sciences de l\u2019activit\u00e9 physique, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"Groupe de recherche en Activit\u00e9 Physique Adapt\u00e9e, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"D\u00e9partement des sciences biologiques, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Mayaki","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre; Department of Critical Care, McGill University Health Centre, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Reynaud","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"D\u00e9partement des sciences de l\u2019activit\u00e9 physique, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"Groupe de recherche en Activit\u00e9 Physique Adapt\u00e9e, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"D\u00e9partement des sciences biologiques, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe E.","family":"Broering","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre; Department of Critical Care, McGill University Health Centre, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-7339","authenticated-orcid":false,"given":"Tomer J.","family":"Chaffer","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre; Department of Critical Care, McGill University Health Centre, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah N. A.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories and Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre; Department of Critical Care, McGill University Health Centre, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-3619","authenticated-orcid":false,"given":"Gilles","family":"Gouspillou","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"D\u00e9partement des sciences de l\u2019activit\u00e9 physique, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"Groupe de recherche en Activit\u00e9 Physique Adapt\u00e9e, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"D\u00e9partement des sciences biologiques, Facult\u00e9 des Sciences, UQAM, Montr\u00e9al, QC H2X 1Y4, Canada"},{"name":"Centre de Recherche de l\u2019Institut Universitaire de G\u00e9riatrie de Montr\u00e9al, Montr\u00e9al, QC H3W 1W5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. 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