PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation
PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation
复制标题
DOI：
10.1007/s13238-019-0618-z
复制
发表时间：
2019-08-01
期刊：
影响因子：
21.1
通讯作者：
Wang, Yiguo
中科院分区：
文献类型：
--
作者：
Li, Tong;Han, Jinbo;Wang, Yiguo
葡萄糖代谢通量从线粒体氧化磷酸化（OXPHOS）到有氧糖酵解的变化被认为是癌症的一个标志。然而，有氧糖酵解和氧化磷酸化之间代谢转换的机制尚不清楚。本研究表明，糖酵解中的限速酶之一丙酮酸激酶（PKM2）的M2异构体与线粒体融合的关键调节因子mitofusin 2 （MFN2）相互作用，促进线粒体融合和OXPHOS，并减弱糖酵解。mTOR通过磷酸化MFN2增加PKM2:MFN2相互作用，从而调节PKM2:MFN2对糖酵解、线粒体融合和OXPHOS的影响。因此，mTOR-MFN2-PKM2信号轴偶联糖酵解和OXPHOS来调节癌细胞的生长。
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.