학술논문
COQ4 is required for the oxidative decarboxylation of the C1 carbon of Coenzyme Q in eukaryotic cells.
Document Type
Author
Pelosi L; Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.; Morbiato L; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Burgardt A; Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.; Tonello F; CNR Institute of Neuroscience, I-35121 Padova, Italy.; Bartlett AK; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.; Guerra RM; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.; Ferizhendi KK; Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.; Desbats MA; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Rascalou B; Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.; Marchi M; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Vázquez-Fonseca L; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Agosto C; Pediatric Pain and Palliative Care Unit, Department of Women and Children's Health, University Hospital of Padova, 35128, Padova, Italy.; Zanotti G; Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35131 Padua, Italy.; Roger-Margueritat M; Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.; Alcázar-Fabra M; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.; García-Corzo L; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.; Sánchez-Cuesta A; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.; Navas P; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.; Brea-Calvo G; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.; Trevisson E; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Wendisch VF; Genetics of Prokaryotes, Faculty of Biology and Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany.; Pagliarini DJ; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.; Salviati L; Clinical Genetics Unit, Department of Women and Children's Health, University of Padova, 35128, Padova, Italy.; Istituto di Ricerca Pediatrica Città della Speranza, 35127, Padova, Italy.; Study Center for Neurodegeneration (CESNE), University of Padua, Padua 35131, Italy.; Lead contact.; Pierrel F; Université Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, TIMC, 38000 Grenoble, France.
Source
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Coenzyme Q (CoQ) is a redox lipid that fulfills critical functions in cellular bioenergetics and homeostasis. CoQ is synthesized by a multi-step pathway that involves several COQ proteins. Two steps of the eukaryotic pathway, the decarboxylation and hydroxylation of position C1, have remained uncharacterized. Here, we provide evidence that these two reactions occur in a single oxidative decarboxylation step catalyzed by COQ4. We demonstrate that COQ4 complements an Escherichia coli strain deficient for C1 decarboxylation and hydroxylation and that COQ4 displays oxidative decarboxylation activity in the non-CoQ producer Corynebacterium glutamicum . Overall, our results substantiate that COQ4 contributes to CoQ biosynthesis, not only via its previously proposed structural role, but also via oxidative decarboxylation of CoQ precursors. These findings fill a major gap in the knowledge of eukaryotic CoQ biosynthesis, and shed new light on the pathophysiology of human primary CoQ deficiency due to COQ4 mutations.
Competing Interests: DECLARATION OF INTERESTS None of the authors have competing interests to disclose.
Competing Interests: DECLARATION OF INTERESTS None of the authors have competing interests to disclose.