MAPL loss dysregulates bile and liver metabolism in mice

ABSTRACT: Mitochondrial and peroxisomal anchored protein ligase (MAPL) is a dual ubiquitin and small ubiquitin-like modifier (SUMO) ligase with roles in mitochondrial quality control, cell death and inflammation in cultured cells. Here, we show that MAPL function in the organismal context converges on metabolic control, as knockout mice are viable, insulin sensitive, and protected from diet induced obesity. MAPL loss leads to liver-specific activation of the integrated stress response, inducing secretion of stress hormone FGF21. MAPL knockout mice develop fully penetrant spontaneous hepatocellular carcinoma. Mechanistically, the peroxisomal bile acid transporter ABCD3 is a primary MAPL interacting partner, and SUMOylated in a MAPL-dependent manner. MAPL knockout leads to increased bile acid producti

SUBMITTER: Dr. Vanessa Goyon 

PROVIDER: S-SCDT-10_15252-EMBR_202357972 | biostudies-other |

REPOSITORIES: biostudies-other