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Although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of mitoISR. In the absence of FGF21, a large part of the metabolic adaptation to mitochondrial dysfunction (one-carbon metabolism, transsulfuration, and serine and proline biosynthesis) is strongly blunted, independent of the primary mitoISR activator ATF4. Collectively, our work highlights the complexity of mitochondrial stress responses by revealing the importance of the tissue specificity and dose dependency of mitoISR.<\/jats:p>","DOI":"10.1126\/sciadv.abn7105","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T17:52:26Z","timestamp":1649267546000},"source":"Crossref","is-referenced-by-count":57,"title":["FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5797-5413","authenticated-orcid":true,"given":"Marijana","family":"Croon","sequence":"first","affiliation":[{"name":"Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, D-50931 Cologne, Germany."},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, 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