Furthermore, our finding that pharmacological inhibition of aberrant mitochondrial Ca2+ accumulation improved survival in the Tfam KO mouse model of lethal mitochondrial myopathy supports a scheme where the adverse effects of ECM perturbations are mediated, at least in part, via impaired Ppif-dependent fine-tuning of cytosolic-mitochondrial Ca2+ fluxes, thus providing a molecular explanation for prolonged survival previously reported when Tfam KO mice were treated with CsA,43 as well as treatment with the more specific cyclophilin inhibitor NV556 used in the present study. Here, PPIF is linked to Mitochondrial myopathy.