{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T13:26:41Z","timestamp":1782221201856,"version":"3.54.5"},"reference-count":194,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-75-10048"],"award-info":[{"award-number":["23-75-10048"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mechanical unloading of skeletal muscle triggers various signaling alterations that result in muscle atrophy and weakness. Mitochondria are essential to muscle health, acting not only as energy suppliers but also as central mediators of molecular regulation. Mitochondrial activity, content, and dynamics are tightly controlled by multiple signaling pathways; conversely, mitochondria-derived messengers, such as reactive oxygen species (ROS), ATP, and mitokines, are involved in the regulation of nearly all aspects of muscle signaling. During mechanical unloading, altered muscle activity leads to mitochondrial dysfunction. However, the initial triggers, underlying mechanisms, and full consequences of this dysfunction remain poorly understood. Nevertheless, mitochondria-targeted therapies have emerged as a promising strategy for mitigating unloading-induced muscle impairments. In this review, we summarize current data regarding the characteristics, causes, and outcomes of unloading-induced mitochondrial dysfunction, specifically focusing on muscle atrophy and functional decline. We highlight novel findings regarding the roles of mitokines and mitochondrial calcium overload, propose a new hypothesis to explain the biphasic dynamics of ATP accumulation during slow-type muscle unloading, and describe emerging therapeutic strategies to counteract these mitochondrial impairments.<\/jats:p>","DOI":"10.3390\/antiox15030277","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T15:05:27Z","timestamp":1771945527000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial Impairment in Unloaded Postural Muscle: Mechanisms Driving Loss of Muscle Function and Mass"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-6312","authenticated-orcid":false,"given":"Kristina A.","family":"Sharlo","sequence":"first","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems RAS, Moscow 123007, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1986-6221","authenticated-orcid":false,"given":"Timur M.","family":"Mirzoev","sequence":"additional","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems RAS, Moscow 123007, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris S.","family":"Shenkman","sequence":"additional","affiliation":[{"name":"Myology Laboratory, Institute of Biomedical Problems RAS, Moscow 123007, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/jappl.2000.89.1.81","article-title":"Skeletal muscle mass and distribution in 468 men and women aged 18\u201388 yr","volume":"89","author":"Janssen","year":"2000","journal-title":"J. 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