Mourier 2015 J Cell Biol

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Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG (2015) Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol 208:429-42.

» PMID:25688136

Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG (2015) J Cell Biol

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.

Keywords: Amplex Red

O2k-Network Lab: DE Cologne Larsson NG, FR Toulouse Casteilla L


Labels: MiParea: Respiration, mt-Structure;fission;fusion, mt-Membrane, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Heart, Fibroblast  Preparation: Permeabilized cells, Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, Gp, Other combinations  HRR: Oxygraph-2k