title: Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels.
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.
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Arnaud
authors: A
authors: Mourier
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Elisa
authors: E
authors: Motori
authors: Max Planck Institute of Biophysics, 60438 Frankfurt, Germany.
authors: Tobias
authors: T
authors: Brandt
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Marie
authors: M
authors: Lagouge
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Ilian
authors: I
authors: Atanassov
authors: 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.
authors: Anne
authors: A
authors: Galinier
authors: 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.
authors: Gunter
authors: G
authors: Rappl
authors: CECAD Research Center, Lipidomics Facility, University of Cologne, 50931 Cologne, Germany.
authors: Susanne
authors: S
authors: Brodesser
authors: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Kjell
authors: K
authors: Hultenby
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
authors: Christoph
authors: C
authors: Dieterich
authors: Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Larsson@age.mpg.de.
authors: Nils-Göran
authors: NG
authors: Larsson
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D034281:Dynamins / Q000235:genetics; D004579:Electron Transport / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology*; D063154:Mitochondrial Dynamics / Q000502:physiology; D010085:Oxidative Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D013729:Terpenes / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D034741:RNA, Small Interfering; D013729:Terpenes; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins; C024989:coenzyme Q10