Inactivation of Pif1 helicase causes a mitochondrial myopathy in mice

Mutations in genes coding for mitochondrial helicases such as TWINKLE and DNA2 are involved in mitochondrial myopathies with mtDNA instability in both human and mouse. We show that inactivation of Pif1, a third member of the mitochondrial helicase family, causes a similar phenotype in mouse. pif1 −/− animals develop a mitochondrial myopathy with respiratory chain deficiency. Pif1 inactivation is responsible for a deficiency to repair oxidative stress-induced mtDNA damage in mouse embryonic fibroblasts that is improved by complementation with mitochondrial isoform mPif167. These results open new perspectives for the exploration of patients with mtDNA instability disorders.