Article
NADP(+)-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance.
Molecular cell - 19 Nov 2015
Li Feng, He Xiadi, Ye Dingwei, Lin Yan, Yu Hongxiu, Yao Cuifang, Huang Lei, Zhang Jianong, Wang Fang, Xu Sha, Wu Xiaohui, Liu Lixia, Yang Chen, Shi Jiaqi, He Xiaoyang, Liu Jie, Qu Yuanyuan, Guo Fushen, Zhao Jianyuan, Xu Wei, Zhao Shimin
Abstract excerpt
Elucidating the tumorigenic mechanism of R-2-hydroxyglutarate (R-2HG) is critical for determining how NADP(+)-IDH mutations cause cancer. Here we report that R-2HG induces cancerous metabolism and apoptosis resistance through promoting hypersuccinylation. By competitive inhibition of the mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH), R-2HG preferentially induced succinyl-CoA...
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