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Although multiple lipid species, including phospholipids, ceramides, triglycerides, and free fatty acids, are susceptible to oxidation, the specific lipid species that drive disease development remain poorly defined. Lipid oxidation is primarily initiated and propagated by reactive oxygen species (ROS). ROS are highly reactive molecules that participate in diverse and complex intracellular signaling pathways. Ferroptosis is a recently identified form of regulated, non-apoptotic cell death characterized by iron-dependent accumulation of lipid peroxides, especially the peroxidation of polyunsaturated fatty acids in cellular membranes, ultimately leading to loss of membrane integrity. Oxidized phospholipids are considered key execution factors in ferroptosis, suggesting an important role for lipid peroxidation in maintaining physiological homeostasis across multiple organs. Our group recently demonstrated that oxidized phospholipids could serve as a source of ROS, thereby promoting muscle atrophy. In the present review, we summarize emerging evidence that membrane lipids, particularly oxidation of phospholipids and polyunsaturated fatty acids, contribute to the generation and propagation of cellular ROS, ultimately facilitating muscle atrophy.<\/jats:p>","DOI":"10.1042\/cs20260445","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:23:00Z","timestamp":1783675380000},"page":"1617-1633","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of central regulators in lipid hydroperoxide-mediated muscle atrophy. Exploring mechanisms beyond ferroptosis"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7558-1098","authenticated-orcid":false,"given":"Hiroaki","family":"Eshima","sequence":"first","affiliation":[{"name":"Department of International Tourism, Nagasaki International University, Sasebo, Nagasaki 8593298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"2026071005225922400_B1","doi-asserted-by":"publisher","first-page":"1225578","DOI":"10.1155\/2022\/1225578","article-title":"ROS: basic concepts, sources, cellular signaling, and its implications in aging pathways","volume":"2022","author":"de Almeida","year":"2022","journal-title":"Oxid. Med. 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