Mitochondrial peptide Mtln contributes to oxidative metabolism in mice

Mitoregulin (Mtln) is a recently identified 56 amino acid long mitochondrial peptide conserved in vertebrates. Mtln is known to enhance function of respiratory complex I, which is likely mediated by modulation of lipid composition. To address an influence of Mtln gene on the metabolism we created knockout mice deficient in Mtln gene. In line with accumulation of triglycerides observed earlier on a model of Mtln knockout cell lines, we observed Mtln KO mice to develop obesity on a high fat diet. An increased weight gain could be attributed to enhanced fat accumulation according to the magnetic resonance live imaging. In addition, Mtln KO mice demonstrate elevated serum triglycerides and other oxidation substrates accompanied by an exhaustion of tricarboxylic acids cycle intermediates, suggesting suboptimal oxidation of respiration substrates by mitochondria lacking Mtln.