title: The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/- mice.
abstract: Mclk1 (also known as Coq7) and Coq3 code for mitochondrial enzymes implicated in the biosynthetic pathway of ubiquinone (coenzyme Q or UQ). Mclk1(+/-) mice are long-lived but have dysfunctional mitochondria. This phenotype remains unexplained, as no changes in UQ content were observed in these mutants. By producing highly purified submitochondrial fractions, we report here that Mclk1(+/-) mice present a unique mitochondrial UQ profile that was characterized by decreased UQ levels in the inner membrane coupled with increased UQ in the outer membrane. Dietary-supplemented UQ(10) was actively incorporated in both mitochondrial membranes, and this was sufficient to reverse mutant mitochondrial phenotypes. Further, although homozygous Coq3 mutants die as embryos like Mclk1 homozygous null mice, Coq3(+/-) mice had a normal lifespan and were free of detectable defects in mitochondrial function or ubiquinone distribution. These findings indicate that MCLK1 regulates both UQ synthesis and distribution within mitochondrial membranes.
authors.affiliation: Department of Biology, McGill University, Montréal, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lapointe
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Eve
authors.initials: E
authors.lastname: Bigras
authors.forename: Siegfried
authors.initials: S
authors.lastname: Hekimi
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D010101:Oxygen Consumption / Q000235:genetics*; D013367:Submitochondrial Particles / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C028325:ubiquinone Q3; D014451:Ubiquinone; D006899:Mixed Function Oxygenases; C434481:Coq7 protein, mouse; C025204:Ubiquinone Q2; C030571:ubiquinone 9