title: Coenzyme Q biosynthesis in health and disease.
abstract: Coenzyme Q (CoQ, or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant. CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ, but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7. Mutations in human COQ genes cause primary CoQ(10) deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy. The pathogenesis of CoQ(10) deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ(10) function are implicated. CoQ(10) deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQ(10) supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy.
authors.forename: Manuel Jesús
authors.initials: MJ
authors.lastname: Acosta
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy.
authors.forename: Luis
authors.initials: L
authors.lastname: Vazquez Fonseca
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy.
authors.forename: Maria Andrea
authors.initials: MA
authors.lastname: Desbats
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cerqua
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Zordan
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy. Electronic address: eva.trevisson@unipd.it.
authors.forename: Eva
authors.initials: E
authors.lastname: Trevisson
authors.affiliation: Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, and IRP Città della Speranza, Padova, Italy. Electronic address: leonardo.salviati@unipd.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
mesh_terms: D000255:Adenosine Triphosphate / Q000819:agonists / Q000096:biosynthesis / Q000172:deficiency; D000818:Animals; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018908:Muscle Weakness / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009154:Mutation; D055503:Protein Multimerization; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000255:Adenosine Triphosphate
keywords: Coenzyme Q; Coenzyme Q10 deficiency; Mitochondrial disorders; Steroid resistant nephrotic syndrome; Ubiquinone