PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation

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.

mTORC1 signaling in hepatic lipid metabolism

The mechanistic target of rapamycin (mTOR) signaling pathway regulates many metabolic and physiological processes in different organs or tissues. Dysregulation of mTOR signaling has been implicated in many human diseases including obesity, diabetes, cancer, fatty liver diseases, and neuronal disorders. Here we review recent progress in understanding how mTORC1 (mTOR complex 1) signaling regulates lipid metabolism in the liver.

Inhibition of proprotein convertases by mung bean trypsin inhibitor / 第二军医大学学报

Objective:To extract the mung bean trypsin inhibitor(MBTI) from mung bean and to study the inhibitory activity of MBTI against proprotein convertases(PCs).Methods: MBTI was purified to homogeneity by ammonium sulfate precipitation, sequential chromatography of gel filtration,ion exchange,affinity chromatography and HPLC.The high expression strains of 2 PCs,Kexin and Furin,were selected.Kexin and Furin were purified by ammonium sulfate precipitation and gel filtration.The inhibitory activity of MBTI against Kexin and Furin was assayed and the inhibitory constants(Ki) of MBTI against the 2 PCs were calculated by Dixon's plot.Results:The purified MBTI showed a single peak on HPLC and a single band on SDS-PAGE.The inhibitory activity of MBTI against Kexin(Ki= 3.9?10~(-9)mol/L) was stronger than that against Furin.Conclusion: MBTI can inhibit both Kexin and Furin,especially Kexin,and also can be an ideal inhibitor against PCs after further modification.