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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,9,26]]},"abstract":"<jats:p>\n                    Mammalian\n                    <jats:italic>FNDC5<\/jats:italic>\n                    encodes a protein precursor of Irisin, which is important for exercise-dependent regulation of whole-body metabolism. In a genetic screen in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , we identified\n                    <jats:italic>Iditarod<\/jats:italic>\n                    (\n                    <jats:italic>Idit<\/jats:italic>\n                    ), which shows substantial protein homology to mouse and human\n                    <jats:italic>FNDC5<\/jats:italic>\n                    , as a regulator of autophagy acting downstream of Atg1\/Atg13. Physiologically,\n                    <jats:italic>Idit<\/jats:italic>\n                    -deficient flies showed reduced exercise performance and defective cold resistance, which were rescued by exogenous expression of\n                    <jats:italic>Idit<\/jats:italic>\n                    . Exercise training increased endurance in wild-type flies, but not in\n                    <jats:italic>Idit<\/jats:italic>\n                    -deficient flies. Conversely, Idit is induced upon exercise training, and transgenic expression of\n                    <jats:italic>Idit<\/jats:italic>\n                    in wild-type flies increased endurance to the level of exercise trained flies. Finally,\n                    <jats:italic>Idit<\/jats:italic>\n                    deficiency prevented both exercise-induced increase in cardiac Atg8 and exercise-induced cardiac stress resistance, suggesting that cardiac autophagy may be an additional mechanism by which\n                    <jats:italic>Idit<\/jats:italic>\n                    is involved in the adaptive response to exercise. Our work suggests an ancient role of an Iditarod\/Irisin\/FNDC5 family of proteins in autophagy, exercise physiology, and cold adaptation, conserved throughout metazoan species.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2220556120","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T15:12:07Z","timestamp":1695049927000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["<i>Iditarod<\/i>\n                    , a\n                    <i>Drosophila<\/i>\n                    homolog of the Irisin precursor\n                    <i>FNDC5<\/i>\n                    , is critical for exercise performance and cardiac autophagy"],"prefix":"10.1073","volume":"120","author":[{"given":"Tyler","family":"Cobb","sequence":"first","affiliation":[{"name":"Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; 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