二氢硫辛酰转乙酰基酶通过乙酰化磷酸葡糖酸脱氢酶促进核酸合成

丙酮酸脱氢酶复合物(pyruvate dehydrogenase complex,PDC)是位于线粒体内的多酶复合物,催化丙酮酸不可逆地氧化脱羧转为乙酰辅酶A,二氢硫辛酰转乙酰基酶(dihydrolipoyl acetyltransferase,DLAT)是PDC的1个亚基.PDC在细胞线粒体呼吸中发挥关键作用.但是D...

Dihydrolipoamide Acetyltransferase Promotes Nucleic Acid Synthesis by Controlling Phosphogluconate Dehydrogenase Acetylation

Mitochondrial pyruvate dehydrogenase complex (PDC) is crucial for glucose homeostasis in mammalian cells, decarboxylation of glycolytic intermediate pyruvate to acetyl coenzyme A (acetyl-CoA) in mitochondria. Dihydrolipoyl acetyltransferase (DLAT) is a subunit of the pyruvate dehydrogenase complex. Here, we reported that DLAT was commonly increased in lung cancer and its expression was associated with worse clinical outcomes. We found that suppression of DLAT in lung cancer cells resulted in reduced nucleic acid biosynthesis and attenuated cancer cell proliferation through controlling acetylation level of 6-phosphogluconate dehydrogenase (6PGD), the third enzyme in the oxidative pentose phosphate pathway (PPP), in which ribulose-5-phosphate (Ru-5-P) is produced for nucleic acid biosynthesis. Together, our study contributes to recent interest and discussion cross talk in cancer metabolism, which contributes to tumor growth. Future mechanistic studies should lead to the elucidation of the mode of action of DLAT in human lung cancer and establish DLAT as a viable drug target.