Coenzyme Q biosynthesis in health and disease

Biochim Biophys Acta. 2016 Aug;1857(8):1079-1085. doi: 10.1016/j.bbabio.2016.03.036. Epub 2016 Apr 7.


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.

Keywords: Coenzyme Q; Coenzyme Q10 deficiency; Mitochondrial disorders; Steroid resistant nephrotic syndrome; Ubiquinone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / agonists
  • Adenosine Triphosphate / biosynthesis
  • Adenosine Triphosphate / deficiency
  • Animals
  • Ataxia / drug therapy
  • Ataxia / genetics
  • Ataxia / metabolism*
  • Ataxia / physiopathology
  • Electron Transport
  • Electron Transport Chain Complex Proteins / genetics
  • Electron Transport Chain Complex Proteins / metabolism*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Diseases / physiopathology
  • Muscle Weakness / drug therapy
  • Muscle Weakness / genetics
  • Muscle Weakness / metabolism*
  • Muscle Weakness / physiopathology
  • Mutation
  • Protein Multimerization
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Ubiquinone / biosynthesis*
  • Ubiquinone / deficiency*
  • Ubiquinone / genetics
  • Ubiquinone / metabolism
  • Ubiquinone / therapeutic use


  • Electron Transport Chain Complex Proteins
  • Reactive Oxygen Species
  • Ubiquinone
  • Adenosine Triphosphate

Supplementary concepts

  • Coenzyme Q10 Deficiency