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

Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels.

Author information

1
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
2
Max Planck Institute of Biophysics, 60438 Frankfurt, Germany.
3
STROMALab, UMR Université Paul Sabatier/Centre National de la Recherche Scientifique 5273, Institut National de la Santé et de la Recherche Médicale U1031, BP 84 225-F-31 432, Toulouse, France.
4
Department I of Internal Medicine, University Hospital Cologne, and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany Department I of Internal Medicine, University Hospital Cologne, and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.
5
CECAD Research Center, Lipidomics Facility, University of Cologne, 50931 Cologne, Germany.
6
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
7
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Larsson@age.mpg.de.

Abstract

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.

PMID:
25688136
PMCID:
PMC4332246
DOI:
10.1083/jcb.201411100
[Indexed for MEDLINE]
Free PMC Article

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