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Desbats 2016 Abstract Mito Xmas Meeting Innsbruck

From Bioblast
CoQ biosynthetic proteins are physically and functionally related to respiratory supercomplexes in mammalian cells.

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Desbats MA, Cogliati S, Corrado M, Rodriguez-Hernandez MA, Trevisson E, Enriquez JA, Navas P, Scorrano L, Salviati L (2016)

Event: Mito Xmas Meeting 2016 Innsbruck AT

Coenzyme Q (CoQ) biosynthesis is a complex process that requires at least 16 different polypeptides. Most CoQ biosynthetic proteins in yeast are organized in a mitochondrial multienzymatic complex (QBC) necessary for CoQ biosynthesis. Coq4p is a component of the Q complex that lacks enzymatic activity which is yet essential for the stability of the complex. However, little is known about the nature of the QBC in mammals. Here, we report that human COQ proteins are localized in the mitochondrial matrix and interact forming several mitochondrial complexes. Interestingly, COQ4 and other COQ polypeptides were found co-migrating with respiratory supercomplexes (RCS) by 1stBN-PAGE-2ndSDS-PAGE/WB. Moreover, COQ4 immunoprecipitated with proteins from complexes I, III and IV, suggesting that the QBC and RCS are structurally related to each other. Strickingly, cells showing defects in RCS biogenesis presented a disruption of the QBC and a decrease in CoQ levels, meaning that supercomplexes are required for efficient CoQ biosynthesis. Conversely, CoQ deficiency in human cells decreased RCS. Finally, CoQ10 supplementation in patient fibroblasts with primary CoQ deficiency increased supercomplexes. Our findings demonstrate the importance of CoQ for supercomplexes biogenesis and suggest the interdependency between CoQ biosynthesis and the respiratory chain organization into RCS in mammalian cells.


Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression, Patients  Pathology: Inherited, Myopathy, Neurodegenerative  Stress:Mitochondrial disease  Organism: Human, Mouse  Tissue;cell: HEK, Fibroblast  Preparation: Homogenate  Enzyme: Complex I, Complex III, Complex IV;cytochrome c oxidase, Supercomplex  Regulation: Aerobic glycolysis 


Event: Poster  Labelled by author 

Affiliations

Desbats MA (1), Cogliati S(2,3), Corrado M(2,4), Rodriguez-Hernández MA(3), Trevisson E(1), Enriquez JA(5), Navas P(4), Scorrano L(2,4), Salviati L(1)
  1. Clinical Genetics Unit, Dept Women Child Health, Univ Padua, Italy
  2. Dulbecco-Telethon Inst, Venetian Inst Molecular Medicine, Padua, Italy
  3. Centro Andaluz de Biología del Desarrollo, Univ Pablo de Olavide, Sevilla, Spain
  4. Dept Biology, Univ Padua, Italy
  5. Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain