SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation

•The expression of SIRT4 is down-regulated in intestinal fibrosis.•SIRT4 provides protection against intestinal fibrosis.•SIRT4 restricts glutaminolysis to reduce extracellular matrix (ECM) deposition.•SIRT4 facilitates glutaminase 1 (GLS1) degradation by hindering SIRT5’s stabilizing interaction with GLS1.•The “α-KG/H3K27me3” signals mediate SIRT4-limited transcription of components in ECM after inhibiting glutaminolysis.