{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:19:56Z","timestamp":1791987596781,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 2018\u2014ID. 21963 project"],"award-info":[{"award-number":["IG 2018\u2014ID. 21963 project"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"publisher","award":["Ex-60% funds"],"award-info":[{"award-number":["Ex-60% funds"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","award":["V2017-021"],"award-info":[{"award-number":["V2017-021"]}],"id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["132013-RSG-18-010-01-CCG"],"award-info":[{"award-number":["132013-RSG-18-010-01-CCG"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative capacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy\/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metabolome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism\/catabolism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted.<\/jats:p>","DOI":"10.3390\/cancers13040850","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-9024","authenticated-orcid":false,"given":"Riccardo","family":"Ballar\u00f2","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy"},{"name":"Interuniversity Institute of Myology, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3475-7485","authenticated-orcid":false,"given":"Patrizia","family":"Lopalco","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-4175","authenticated-orcid":false,"given":"Valentina","family":"Audrito","sequence":"additional","affiliation":[{"name":"Molecular Biotechnology Center, University of Torino, 10125 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6070-9861","authenticated-orcid":false,"given":"Marc","family":"Beltr\u00e0","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy"},{"name":"Interuniversity Institute of Myology, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Pin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology and Physiology, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5136-5921","authenticated-orcid":false,"given":"Roberto","family":"Angelini","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Costelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy"},{"name":"Interuniversity Institute of Myology, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9658-8520","authenticated-orcid":false,"given":"Angela","family":"Corcelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-1871","authenticated-orcid":false,"given":"Andrea","family":"Bonetto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazel H.","family":"Szeto","sequence":"additional","affiliation":[{"name":"Social Profit Network Research Lab, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4342-9539","authenticated-orcid":false,"given":"Thomas M.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-6027","authenticated-orcid":false,"given":"Fabio","family":"Penna","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10125 Torino, Italy"},{"name":"Interuniversity Institute of Myology, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. 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