Crotonylation of IDH1 alleviates MASLD progression by enhancing the TCA cycle.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD), potentially ameliorated by bariatric-metabolic surgery, remains a global health concern in the absence of approved drugs. Protein post-translational modifications (PTMs) are crucial for MASLD. However, the functional significance of lysine crotonylation (Kcr) remains unclear. We aimed to investigate the mechanisms by Kcr-regulated IDH1 in the tricarboxylic acid (TCA) cycle and MASLD development. Herein, we reported a quantitative proteomics analysis of global crotonylome upon MASLD and Post-bariatric. Specifically, decreases in K58cr, K151cr, K212cr and K345cr of IDH1 upon MASLD were observed. PCAF and SIRT7 dynamically regulated the IDH1 Kcr. Abolishment of IDH1 Kcr impaired TCA cycle by decreasing IDH1 enzymatic activity.

SUBMITTER: Liu S 

PROVIDER: S-EPMC12381242 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature