摘要Dear Editor,Lysine residue succinylation is a novel post-translational modification that recently attracted extensive attention. Succinylation is achieved by non-enzymatic processes or by a series of enzymes [like p300, lysine acetyltransferase 2A (KAT2A)] that transfer the succinyl groups from succinyl-coenzyme A (CoA) to the specific lysine, modulating protein function in various physiological processes[1]. As a high-energy metabolite, succinyl-CoA is mainly produced within the mitochondrial matrix and peroxisomes. Its high-rate generation in the tricarboxylic acid (TCA) cycle and its impermeability across the mitochondrial inner membrane (due to its negative charge property) enhance succinyl-CoA accumulation within mitochondria. It is therefore not surprising that mitochondrial proteins have a higher potential to be succinylated, although succinylation has been reported to be accumulated at transcriptional starting sites, modulating histones to regulate gene expression. Being a key component of the TCA cycle, the α-ketoglutarate dehydrogenase (α-KGDH) complex as the key source of succinyl-CoA has been found to interact with KAT2A in the nucleus for mediating histone succinylation on H3K79. Notably, only 1.0％–1.6％ of the α-KGDH complex is located in the nucleus, which consequently contributes to histone succinylation[2].