GCDH Acetylation Orchestrates DNA Damage Response and Autophagy via Mitochondrial ROS to Suppress Hepatocellular Carcinoma Progression.

ABSTRACT: Metabolic enzyme dysregulation promotes hepatocellular carcinoma (HCC) progression through metabolic reprogramming and lysine acetylation. Glutaryl-CoA dehydrogenase (GCDH), a key enzyme in lysine metabolism, has been demonstrated to play an essential role in modulating lysine crotonylation, which impacts the progression of HCC. However, the specific mechanisms by which GCDH influences lysine acetylation in HCC have not been completely clarified. In this study, GCDH was found to be acetylated at lysine 438 by acetyltransferase P300 and deacetylated by HDAC1. GCDH K438 acetylation was critical for its tumor-suppressive function in HCC cells. Overexpression of GCDH led to elevated levels of reactive oxygen species (ROS) and reduced oxidative phosphorylation (OXPHOS), thereby triggering ATR/C

SUBMITTER: Tian W 

PROVIDER: S-EPMC12395558 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature