Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels

J Cell Biol. 2015 Feb 16;208(4):429-42. doi: 10.1083/jcb.201411100.


Mitochondria form a dynamic network within the cell as a result of balanced fusion and fission. Despite the established role of mitofusins (MFN1 and MFN2) in mitochondrial fusion, only MFN2 has been associated with metabolic and neurodegenerative diseases, which suggests that MFN2 is needed to maintain mitochondrial energy metabolism. The molecular basis for the mitochondrial dysfunction encountered in the absence of MFN2 is not understood. Here we show that loss of MFN2 leads to impaired mitochondrial respiration and reduced ATP production, and that this defective oxidative phosphorylation process unexpectedly originates from a depletion of the mitochondrial coenzyme Q pool. Our study unravels an unexpected and novel role for MFN2 in maintenance of the terpenoid biosynthesis pathway, which is necessary for mitochondrial coenzyme Q biosynthesis. The reduced respiratory chain function in cells lacking MFN2 can be partially rescued by coenzyme Q10 supplementation, which suggests a possible therapeutic strategy for patients with diseases caused by mutations in the Mfn2 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Cells, Cultured
  • Dynamins / genetics
  • Electron Transport / genetics*
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / enzymology*
  • Mitochondrial Dynamics / physiology
  • Oxidative Phosphorylation
  • RNA Interference
  • RNA, Small Interfering
  • Terpenes / metabolism
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / biosynthesis


  • RNA, Small Interfering
  • Terpenes
  • Ubiquinone
  • Adenosine Triphosphate
  • GTP Phosphohydrolases
  • Mfn1 protein, mouse
  • Mfn2 protein, mouse
  • Dnm1l protein, mouse
  • Dynamins
  • coenzyme Q10