Hepatocyte selective Optic Atrophy 1 (OPA1) deficiency limits obesity development and hepatic steatosis by affecting lipid absorption via reduced bile acids conjugation as a consequence of decreased mitochondrial-peroxisome-ER axis function.

Mitochondria are constantly undergoing biogenesis, fusion, fission, and mitophagy, ensuring a constant balance between all forms. We investigated the effect of a selective deficiency of OPA1, a protein involved in the fusion of the inner mitochondria membrane, on metabolic lipid disorders in the liver. RNAseq and proteomic analysis revealed that this was due to a change in the mitochondrial-peroxisome-ER axis in hepatocytes, which resulted in hepatic retention of unconjugated bile acids.