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.

Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts

“…CoQ 10 plays a crucial role in mitochondrial bioenergetics and can act as an antioxidant [7,36]. However, CoQ 10 as a determinant of muscular strength is not well documented.…”

Mitochondrial energy generation disorders: genes, mechanisms, and clues to pathology

“…2). Individual references for genes are listed in Table S1 or detailed in the following reviews (19,20,(25)(26)(27)(28)(29).…”

“…The largest group of primary defect genes encode structural subunits of one of the five OXPHOS complexes, factors required for their assembly, or are involved in the biogenesis of the electron carriers cytochrome c and ubiquinone (coenzyme Q; CoQ) (19,26,28). Probably due to its large size (1MDa) and complexity, the majority of genes in this category are subunits or assembly factors of OXPHOS complex I (NADH:ubiquinone oxidoreductase), with mutations now identified in all 14 subunits of its catalytic core, along with 13 of the 30 accessory subunits, and 11 of at least 15 assembly factors (19,(39)(40)(41).…”

Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects

“…Some p -quinones can be crystallized ( t -butylquinone, menadione), and there are examples of natural products with stable p -quinone structures (e.g., juglone, ansamycin antibiotics) as well as endogenous compounds (vitamin K, ubiquinone) (Table 1). 10−14 Ubiquinone is an antioxidant in the mitochondria, and its analogues could be useful for the treatment of both Alzheimer’s and Parkinson’s disease since mitochondrial failure, often due to ROS, is involved in the progression of both neurodegenerative diseases. 15−17 Mitoquinone is a ubiquinone analogue in clinical trials for the treatment of Parkinson’s disease.…”