{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T17:14:13Z","timestamp":1784049253281,"version":"3.55.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR-INMD"],"award-info":[{"award-number":["CIHR-INMD"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000035","name":"Institute of Nutrition, Metabolism and Diabetes","doi-asserted-by":"publisher","award":["FDN-143278"],"award-info":[{"award-number":["FDN-143278"]}],"id":[{"id":"10.13039\/501100000035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Glutathione is an important antioxidant that regulates cellular redox status and is disordered in many disease states. Glutaredoxin 2 (<jats:italic>Grx2<\/jats:italic>) is a glutathione-dependent oxidoreductase that plays a pivotal role in redox control by catalyzing reversible protein deglutathionylation. As oxidized glutathione (GSSG) can stimulate mitochondrial fusion, we hypothesized that<jats:italic>Grx2<\/jats:italic>may contribute to the maintenance of mitochondrial dynamics and ultrastructure. Here, we demonstrate that<jats:italic>Grx2<\/jats:italic>deletion results in decreased GSH:GSSG, with a marked increase of GSSG in primary muscle cells isolated from C57BL\/6<jats:italic>Grx2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>mice. The altered glutathione redox was accompanied by increased mitochondrial length, consistent with a more fused mitochondrial reticulum. Electron microscopy of<jats:italic>Grx2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>skeletal muscle fibers revealed decreased mitochondrial surface area, profoundly disordered ultrastructure, and the appearance of multi-lamellar structures. Immunoblot analysis revealed that autophagic flux was augmented in<jats:italic>Grx2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>muscle as demonstrated by an increase in the ratio of LC3II\/I expression. These molecular changes resulted in impaired complex I respiration and complex IV activity, a smaller diameter of<jats:italic>tibialis anterior<\/jats:italic>muscle, and decreased body weight in<jats:italic>Grx2<\/jats:italic>deficient mice. Together, these are the first results to show that<jats:italic>Grx2<\/jats:italic>regulates skeletal muscle mitochondrial structure, and autophagy.<\/jats:p>","DOI":"10.3389\/fphys.2021.604210","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T06:54:25Z","timestamp":1614927265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Grx2 Regulates Skeletal Muscle Mitochondrial Structure and Autophagy"],"prefix":"10.3389","volume":"12","author":[{"given":"Ava","family":"Liaghati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal A.","family":"Pileggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaganvir","family":"Parmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Patten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hadzimustafic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexanne","family":"Cuillerier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keir J.","family":"Menzies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Burelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Ellen","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"29857","DOI":"10.1074\/jbc.M313320200","article-title":"S-glutathiolation of Ras mediates redox-sensitive signaling by angiotensin II in vascular smooth muscle cells","volume":"279","author":"Adachi","year":"2004","journal-title":"J. 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