The inhibition of inner mitochondrial fusion in hepatocytes reduces NAFL and improves metabolic profile during obesity by modulating bile acid conjugation.

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.