Cao, YuZhang, MengLi, YeLu, JingjingZhou, WanhuiLi, XiaoshuangShi, HaoXu, BinLi, Shize2022-11-292022-11-292022-11-22Cao, Y.; Zhang, M.; Li, Y.; Lu, J.; Zhou, W.; Li, X.; Shi, H.; Xu, B.; Li, S. O-GlcNAcylation of SIRT1 Protects against Cold Stress-Induced Skeletal Muscle Damage via Amelioration of Mitochondrial Homeostasis. Int. J. Mol. Sci. 2022, 23, 14520.http://hdl.handle.net/10919/112724Cold stress disturbs cellular metabolic and energy homeostasis, which is one of the causes of stress-induced illnesses. O-GlcNAcylation is a nutrient-sensing pathway involved in a myriad of cellular processes. It plays a key role in metabolic homeostasis. Nevertheless, a specific sensing mechanism linking skeletal muscle to O-GlcNAcylation in cold stress is unknown. In this study, O-GlcNAcylation of SIRT1 was targeted to explore the mechanism of skeletal muscle adaptation to cold stress. <i>Ogt</i> mKO aggravated skeletal muscle fibrosis induced by cold stress. At the same time, <i>Ogt</i> gene deletion accelerated the homeostasis imbalance and oxidative stress of skeletal muscle mitochondria induced by cold stress. In vitro results showed that inhibition of SIRT1&rsquo;s O-GlcNAcylation accelerated mild hypothermia induced mitochondrial homeostasis in mouse myogenic cells (C2C12 cells). However, overexpression of SIRT1&rsquo;s O-GlcNAcylation improved the above phenomena. Thus, these results reveal a protective role of OGT-SIRT1 in skeletal muscle&rsquo;s adaptation to cold stress, and our findings will provide new avenues to combat stress-induced diseases.application/pdfenCreative Commons Attribution 4.0 Internationalcold stressskeletal musclemetabolic homeostasis imbalanceSIRT1O-GlcNAcylationArticle - Refereed2022-11-24https://doi.org/10.3390/ijms232314520