Dihydrolipoamide Acetyltransferase Promotes Nucleic Acid Synthesis by Controlling Phosphogluconate Dehydrogenase Acetylation / 中国生物化学与分子生物学报

ABSTRACT

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.