Coenzyme Q Biosynthesis Disorders

Coenzyme Q (CoQ) is a lipidic molecule that transfers electrons between complexes I and II to complex III in the mitochondrial respiratory chain. It is also essential for processes mediated by other mitochondrial dehydrogenases, such as those involved in pyrimidine nucleotides biosynthesis, beta-oxidation and sulfide biosynthesis. A nuclear-encoded multiprotein complex at the inner mitochondrial membrane drives CoQ biosynthesis, which requires at least 13 proteins, leastways in yeasts. Mutations in the genes (COQ genes) coding for these proteins cause a decrease of CoQ biosynthesis rate leading to primary CoQ deficiency, a very heterogeneous group of mitochondrial diseases affecting different tissues and organs, and showing variable severity and age of onset. In general, this primary condition shows a good response to the supplementation with high doses of CoQ, but early diagnosis is compulsory to limit tissue damage. However, sometimes effectiveness is reduced, possibly due to its low bioavailability and, probably, difficulties crossing the blood-brain barrier. Secondary CoQ deficiency is a more common condition, in which defects of diverse mitochondrial processes induce an adaptive CoQ decrease. Secondary deficiency can be caused by oxidative phosphorylation (OXPHOS) defects, such as complex III dysfunction or mitochondrial DNA (mtDNA) depletion, or even non-OXPHOS mitochondrial defects. Here, we review the current knowledge of CoQ biosynthesis pathway, the genetic defects leading to primary deficiency and those conditions in which mitochondrial defects cause secondary deficiency.