Furthermore, on the mitochondrial side, the MAM-related matrix protein cyclophilin D (also called peptidyl-prolyl cis-trans isomerase F) is involved in excessive Ca2+ uptake, as illustrated by results showing (1) partial inhibition of the uptake by application of the cyclophilin D-binding inhibitor cyclosporine A; (2) increased protein expression of cyclophilin D in skeletal muscle from both Tfam KO mice and mitochondrial myopathy patients; and (3) an increased lifespan of cyclosporine A-treated Tfam KO mice (Aydin et al., 2009; Gineste et al., 2015). This evidence concerns the gene PROS1 and Mitochondrial myopathy.