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Knowledge regarding the mechanism of cancer\u2010induced cachexia remains very scarce, making cachexia an unmet medical need. In this study, we discovered strong alterations of iron metabolism in the skeletal muscle of both cancer patients and tumor\u2010bearing mice, characterized by decreased iron availability in mitochondria. We found that modulation of iron levels directly influences myotube size\n                    <jats:italic>in vitro<\/jats:italic>\n                    and muscle mass in otherwise healthy mice. Furthermore, iron supplementation was sufficient to preserve both muscle function and mass, prolong survival in tumor\u2010bearing mice, and even rescues strength in human subjects within an unexpectedly short time frame. Importantly, iron supplementation refuels mitochondrial oxidative metabolism and energy production. Overall, our findings provide new mechanistic insights in cancer\u2010induced skeletal muscle wasting, and support targeting iron metabolism as a potential therapeutic option for muscle wasting diseases.\n                  <\/jats:p>","DOI":"10.15252\/embr.202153746","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T06:07:20Z","timestamp":1645682840000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Iron supplementation is sufficient to rescue skeletal muscle mass and function in cancer cachexia"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-5396","authenticated-orcid":false,"given":"Elisabeth","family":"Wyart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-7368","authenticated-orcid":false,"given":"Myriam Y","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2763-9838","authenticated-orcid":false,"given":"Roberta","family":"Sartori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Mina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-1197","authenticated-orcid":false,"given":"Elisa S","family":"Pierobon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosa","family":"Mezzanotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Pezzini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-3234","authenticated-orcid":false,"given":"Laure B","family":"Bindels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lauria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Penna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8824-4015","authenticated-orcid":false,"given":"Massimiliano","family":"Mazzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Roetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Geninatti Crich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8802-7352","authenticated-orcid":false,"given":"Hans","family":"Prenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sandri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Menga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-1552","authenticated-orcid":false,"given":"Paolo E","family":"Porporato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"BFEMBR202153746_CR1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.2174\/1389203720666190402100902","volume":"20","author":"J Abrigo","year":"2019","unstructured":"Abrigo J, Simon F, Cabrera D, Vilos C, Cabello\u2010Verrugio C (2019) Mitochondrial dysfunction in skeletal muscle pathologies. 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