Jinbo Han
Liangjie Jia
Xiao Hu
Liqun Chen
Yiguo Wang
MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Funds: We thank Drs. Peng Jiang, Li Yu and Suneng Fu for helpful discussion. This work was supported by grants from the Ministry of Science and Technology of the People's Republic of China (2017YFA0503404 and 2016YFC1304803), and the National Natural Science Foundation of China (Grant Nos. 31625014, 31621063 and 31830040).
Received Date: 2019-02-13
Rev Recd Date:2019-02-26
Abstract
Abstract
A change in the metabolic flux of glucose from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis is regarded as one hallmark of cancer. However, the mechanisms underlying the metabolic switch between aerobic glycolysis and OXPHOS are unclear. Here we show that the M2 isoform of pyruvate kinase (PKM2), one of the rate-limiting enzymes in glycolysis, interacts with mitofusin 2 (MFN2), a key regulator of mitochondrial fusion, to promote mitochondrial fusion and OXPHOS, and attenuate glycolysis. mTOR increases the PKM2:MFN2 interaction by phosphorylating MFN2 and thereby modulates the effect of PKM2:MFN2 on glycolysis, mitochondrial fusion and OXPHOS. Thus, an mTOR-MFN2-PKM2 signaling axis couples glycolysis and OXPHOS to modulate cancer cell growth.Keywords: PKM2,
MFN2,
mTOR,
glycolysis,
oxidative phosphorylation
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