Inactivation of Pif1 helicase causes a mitochondrial myopathy in mice

Mitochondrion. 2016 Sep:30:126-37. doi: 10.1016/j.mito.2016.02.005. Epub 2016 Feb 24.

Abstract

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 mPif1(67). These results open new perspectives for the exploration of patients with mtDNA instability disorders.

Keywords: Mitochondrial disease; Mitochondrial myopathy; Pif1 helicase; mtDNA instability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA Helicases / antagonists & inhibitors*
  • Fibroblasts / physiology
  • Gene Silencing*
  • Mice
  • Mice, Knockout
  • Mitochondrial Diseases
  • Mitochondrial Myopathies / genetics*

Substances

  • DNA Helicases
  • Pif1 protein, mouse