Metabolic Targets of Coenzyme Q10 in Mitochondria

This work was supported by grants from Ministerio de Ciencia e Innovacion, Spain, and the ERDF (RTI2018-093503-B-100), the Muscular Dystrophy Association (MDA-602322). C.M.Q. is supported by the Department of Defense (DOD) grant PR190511. A.H.-G. and P.G.-G. are `FPU fellows' from the Ministerio de Universidades, Spain. S.L.-H. is supported by the "becas de colaboracion" from the Ministerio de Universidades, Spain. E.B.-C. is supported by the Consejeria de Salud, Junta de Andalucia, Spain.

We thank Stacy Kelly Aguirre for the English editing. Figures created with BioRender.com.

Coenzyme Q10 (CoQ(10)) is classically viewed as an important endogenous antioxidant and key component of the mitochondrial respiratory chain. For this second function, CoQ molecules seem to be dynamically segmented in a pool attached and engulfed by the super-complexes I + III, and a free pool available for complex II or any other mitochondrial enzyme that uses CoQ as a cofactor. This CoQ-free pool is, therefore, used by enzymes that link the mitochondrial respiratory chain to other pathways, such as the pyrimidine de novo biosynthesis, fatty acid beta-oxidation and amino acid catabolism, glycine metabolism, proline, glyoxylate and arginine metabolism, and sulfide oxidation metabolism. Some of these mitochondrial pathways are also connected to metabolic pathways in other compartments of the cell and, consequently, CoQ could indirectly modulate metabolic pathways located outside the mitochondria. Thus, we review the most relevant findings in all these metabolic functions of CoQ and their relations with the pathomechanisms of some metabolic diseases, highlighting some future perspectives and potential therapeutic implications.

Spanish Government

European Commission RTI2018-093503-B-100

Muscular Dystrophy Association MDA-602322

United States Department of Defense PR190511

Ministerio de Universidades, Spain

Junta de Andalucia