Zhao 2021 Diabetes
|Zhao Q, Luo T, Gao F, Fu Y, Li B, Shao X, Chen H, Zhou Z, Guo S, Shen L, Jin L, Cen D, Zhou H, Lyu J, Fang H (2021) GRP75 regulates mitochondrial-supercomplex turnover to modulate insulin sensitivity. Diabetes [Epub ahead of print].|
Abstract: GRP75, defined as a major component of both mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both in vitro and in vivo models with insulin resistance. We found that GRP75 was downregulated in HFD-fed mice, and induction of Grp75 in mice could prevent HFD induced obesity and insulin resistance. Mechanistically, GRP75 influenced insulin sensitivity by regulating mitochondrial function through its modulation of mitochondrial-supercomplex turnover rather than MAM communication: GRP75 was negatively associated with respiratory-chain complex activity and was essential for mitochondrial-supercomplex assembly and stabilization. Moreover, mitochondrial dysfunction in Grp75-knockdown cells might further increase mitochondrial fragmentation, thus trigger cytosolic mitochondrial DNA release and activate the cGAS/STING-dependent pro-inflammatory response. Therefore, GRP75 can serve as a potential therapeutic target of insulin resistant-related diabetes or other metabolic diseases.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration