Metabolic dysfunction-associated steatohepatitis reduces hepatic H₂S-producing enzymes altering persulfidome composition.

ABSTRACT: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease driven by obesity-related hepatic inflammation and oxidative stress. Recently, cysteine persulfidation (PSSH), a protective post-translational modification by hydrogen sulfide (H₂S), was established to play a role in redox regulation. Despite the role of the liver in H₂S metabolism, the function of PSSH in MASH remains underexplored. We demonstrated that H₂S-producing enzymes are downregulated in both human and mouse livers with steatosis and fibrosis, resulting in a decline in global PSSH levels. Dimedone-switch mass spectrometry in dietary mouse models of distinct obesity-associated liver disease stages revealed dysregulated PSSH on specific proteins. Surprisingly, increased

SUBMITTER: Shen TK 

PROVIDER: S-EPMC12421645 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature