Succinylation - encoded metabolic codes: cracking the molecular logic of cellular adaptation.

Lysine succinylation is the covalent modification of succinyl groups (-CO-CH ₂ -CH ₂ -COOH) to lysine residues of target proteins, which causes conformational changes and regulates their functional states. In this figure, mitochondria are used as the metabolic hub to summarize the production and consumption of succinyl-CoA in the TCA cycle and mediate the succinylation of key enzymes and transcription factors such as PDH, SDH, GLUD1, HMGCS2, and FEN1. The central region showed the negative regulation of SIRT5/SIRT7 and the positive regulation of KAT2A, alpha-KGDH, CPT1A, HAT1, and other acyltransferases. The lower part of the figure highlights that succinylation promotes tumor cell hypoxic adaptation and immune escape by stabilizing HIF-1α, inducing ROS production, and SDH dysfunction. TCA, Tricarboxylic acid cycle PDH, Pyruvate dehydrogenase SDH, Succinate dehydrogenase GLUD1, Glutamate dehydrogenase 1 HMGCS2, 3-hydroxy-3-methylglutaryl-CoA synthase 2 FEN1, Flap endonuclease 1, SIRT, Sirtuin family proteins, KAT2A, Lysine acetyltransferase 2A alpha-KGDH, Alpha-ketoglutarate dehydrogenase CPT1A, Carnitine palmitoyltransferase 1A HAT1, Histone acetyltransferase 1 HIF-1α, Hypoxia-inducible factor 1 alpha ROS Reactive oxygen species.This figure was created by Biorender.com.(https://BioRender.com).