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PMID: 25688136 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels.

The Journal of cell biology ·Vol. 208 ·No. 4 ·2015-02-16 ·Pages 429-42

Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG

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.

MeSH Terms
Adenosine Triphosphate/biosynthesis Animals Cells, Cultured Dynamins/genetics Electron Transport/genetics Energy Metabolism/genetics,physiology GTP Phosphohydrolases/genetics,physiology Mice Mice, Inbred C57BL Mice, Knockout Mitochondria/enzymology Mitochondrial Dynamics/physiology Oxidative Phosphorylation RNA Interference RNA, Small Interfering Terpenes/metabolism Ubiquinone/analogs & derivatives,biosynthesis
Chemicals
RNA, Small Interfering Terpenes Ubiquinone Adenosine Triphosphate GTP Phosphohydrolases Mfn1 protein, mouse Mfn2 protein, mouse Dnm1l protein, mouse Dynamins coenzyme Q10
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Mourier Arnaud
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Motori Elisa
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Brandt Tobias
Max Planck Institute of Biophysics, 60438 Frankfurt, Germany.
Lagouge Marie
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Atanassov Ilian
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Galinier Anne
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.
Rappl Gunter
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.
Brodesser Susanne
CECAD Research Center, Lipidomics Facility, University of Cologne, 50931 Cologne, Germany.
Hultenby Kjell
Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Dieterich Christoph
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Larsson Nils-Göran
Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Larsson@age.mpg.de.
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201411100
Email
larsson@age.mpg.de
Published
2015-02-16
Pages
429-42
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC4332246
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.201411100 PMC Full Text View journal details
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