Lipid peroxidation does not mediate muscle atrophy induced by PSD deficiency.

Mechanisms by which disuse promotes skeletal muscle atrophy is not well understood. We previously demonstrated that disuse reduces the abundance of mitochondrial phosphatidylethanolamine (PE) in skeletal muscle. Deletion of phosphatidylserine decarboxylase (PSD), an enzyme that generates mitochondrial PE, was sufficient to promote muscle atrophy. In this study, we tested the hypothesis that muscle atrophy induced by PSD deletion is driven by an accumulation of lipid hydroperoxides (LOOH). Mice with muscle-specific knockout of PSD (PSD-MKO) were crossed with glutathione peroxidase 4 (GPx4) transgenic mice (GPx4Tg) to suppress the accumulation of LOOH. However, PSD-MKO × GPx4Tg mice and PSD-MKO mice demonstrated equally robust loss of muscle mass. These results suggest that muscle atrophy induced by PSD deficiency is not driven by the accumulation of LOOH.