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Selenium is an essential trace element that maintains muscle integrity; however, the mechanisms linking Se deficiency to muscle injury remain unclear. Selenoprotein T (SELENOT) is a key regulator of cellular redox homeostasis that has not been fully characterized in skeletal muscles. Se deficiency downregulates SELENOT expression, increases oxidative stress, and induces skeletal muscle atrophy via disulfidase pathways. SELENOT deficiency impaired mitochondrial respiratory chain function, causing mitochondrial reactive oxygen species (mtROS) overproduction, glucose metabolism reprogramming, and Nicotinamide Adenine Dinucleotide Phosphate (NADPH) metabolism disruption. These changes result in cysteine accumulation and disulfidptosis, which lead to abnormal actin disulfide bonding. TEMPO\u2010mediated mtROS inhibition or NADPH supplementation partially rescues Se\u2010deficiency\u2010induced muscle atrophy. SELENOT overexpression alleviates the redox imbalance, NADPH dysfunction, disulfidptosis, and myotube atrophy in Se\u2010deficient cells, whereas rotenone\u2010induced mtROS activation or BAY\u2010876\u2010mediated NADPH inhibition reverses these protective effects. The SELENOT\/mtROS\/NADPH axis is crucial for Se\u2010deficiency\u2010induced muscle atrophy. This study provides mechanistic insights into muscle\u2010wasting disorders and potential therapeutic targets.<\/jats:p>","DOI":"10.1002\/advs.202507283","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T19:30:33Z","timestamp":1757964633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Redox Cascade in Chicken Skeletal Muscle: SELENOT Suppression in Selenium Deficiency Triggers Disulfidptosis via mtROS\u2010NADPH Dysregulation"],"prefix":"10.1002","volume":"12","author":[{"given":"Huanyi","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Northeast Agricultural University  Harbin 150030 P. R. China"},{"name":"Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment College of Veterinary Medicine Northeast Agricultural University  Harbin 150030 P. R. 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