ATP合酶
线粒体
蛋白质亚单位
安普克
生物化学
行动方式
化学
生物
细胞生物学
磷酸化
酶
基因
蛋白激酶A
作者
Haibo Wang,Ligang Hu,Hongyan Li,Yau‐Tsz Lai,Xueying Wei,Xiaohan Xu,Zhenkun Cao,Huiming Cao,Qianya Wan,Yuen‐Yan Chang,Aimin Xu,Qunfang Zhou,Guibin Jiang,Ming‐Liang He,Hongzhe Sun
标识
DOI:10.1038/s41467-023-37351-w
摘要
Abstract Chromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III).
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