Hepatocyte FAM210A deficiency disrupts mitochondrial function and triggers juvenile steatosis with compensatory repair in adulthood

Here, we identify Family with sequence similarity 210 member A (FAM210A) as a hepatocyte-enriched mitochondrial regulator essential for postnatal liver maturation. Hepatocyte-specific deletion of Fam210a (Fam210aHKO) in mice caused early growth restriction, reduced body and liver mass, and pronounced hepatic steatosis with glycogen depletion.

These defects were accompanied by lower postprandial glucose levels in the fastedre–feeding state, impaired oxidative phosphorylation, reduced mtDNA content, and abnormal cristae architecture. Transcriptomic and proteomic profiling revealed broad suppression of fatty acid, sterol, and bile acid metabolism, with concomitant glutathione stress responses. Mechanistically, FAM210A deficiency induces excessive OPA1 cleavage and cristae destabilization, potentially by disrupting YME1L function.