Disorders of Human Coenzyme Q10 Metabolism: An Overview.

Iain Hargreaves,Robert A Heaton,David Mantle

doi:10.3390/ijms21186695

Iain Hargreaves, Robert A Heaton + Show 1 more

Open Access

https://doi.org/10.3390/ijms21186695

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Abstract

Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extramitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid, pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. In view of the central role of CoQ10 in cellular metabolism, it is unsurprising that a CoQ10 deficiency is linked to the pathogenesis of a range of disorders. CoQ10 deficiency is broadly classified into primary or secondary deficiencies. Primary deficiencies result from genetic defects in the multi-step biochemical pathway of CoQ10 synthesis, whereas secondary deficiencies can occur as result of other diseases or certain pharmacotherapies. In this article we have reviewed the clinical consequences of primary and secondary CoQ10 deficiencies, as well as providing some examples of the successful use of CoQ10 supplementation in the treatment of disease.

Highlights

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule comprising a central benzoquinone moiety, to which is attached a 10-unit polyisoprenoid lipid tail [1] (Figure 1)
CoQ10 serves as an important lipid-soluble antioxidant protecting cellular membranes, both mitochondrial and extra-mitochondrial (Golgi apparatus, lysosomes, endoplasmic reticulum, peroxisomes) from free radical-induced oxidative stresFsi(gOurSe)1[.2T].heInchaedmdiictailosntrtuoctaucrteinofgCaosQa1n0. antioxidant directly, CoQ10 is involved in the regeneration of the antioxidants vitamin C and vitamin E, respectively [4]
Identification of CoQ10 deficiency in patients with cerebellar ataxia is essential, since patients may show remarkable clinical improvement following CoQ10 supplementation when administered at an early stage of disease [67]

Summary

Introduction

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule comprising a central benzoquinone moiety, to which is attached a 10-unit polyisoprenoid lipid tail [1] (Figure 1). CoQ10 serves as an important lipid-soluble antioxidant protecting cellular membranes, both mitochondrial and extra-mitochondrial (Golgi apparatus, lysosomes, endoplasmic reticulum, peroxisomes) from free radical-induced oxidative stresFsi(gOurSe)1[.2T].heInchaedmdiictailosntrtuoctaucrteinofgCaosQa1n0. CoQ10 has a key role as an electron carrier (from complex I and II to complex III) in the mitochondrial electron transport chain (METC) during oxidative phosphorylation (Figure 2) It is involved (as a cofactor of the enzyme dihydroorate dehydrogenase) in the metabolism of pyrimidines, fatty acids and mitochondrial uncoupling proteins, as well as in the regulation of the mitochondrial permeability transition pore [1]. CoQ10 serves as an important lipid-soluble antioxidant protecting cellular membranes, both mitochondrial and extra-mitochondrial (Golgi apparatus, lysosomes, endoplasmic reticulum, peroxisomes) from free radical-induced oxidative stress (OS) [2]. Mutations in 10 of these genes have been identified to date: the corresponding gene products respectively are PDSS1 (phenyl diphosdphate synthase subunit 1; [27]), PDSS2 (decaprenyl diphosphate synthase subunit 2; [28]) COQ4 (multienzyme complex organisation enzyme; [29]), COQ5 (methyltransferase; [30]), COQ6 (monooxygenase; [31]), COQ7 (DMG hydroxylase; [32], ADCK3 (renamed COQ8A, protein kinase; [33]), ADCK4 (renamed COQ8B, protein kinase; [34]) and COQ9 (lipid-binding protein; [35])

Secondary CoQ10 Deficiency

Clinical Assessment of CoQ10

Findings

Conclusions