Coenzyme Q biosynthesis and its role in the respiratory chain structure

Abstract

Coenzyme Q (CoQ) is a unique electron carrier in the mitochondrial respiratory chain, which is synthesized on-site by a nuclear encoded multiprotein complex. CoQ receives electrons from different redox pathways, mainly NADH and FADH2 from tricarboxylic acid pathway, dihydroorotate dehydrogenase, electron transfer flavoprotein dehydrogenase and glycerol-3-phosphate dehydrogenase that support key aspects of the metabolism. Here we explore some lines of evidence supporting the idea of the interaction of CoQ with the respiratory chain complexes, contributing to their superassembly, including respirasome, and its role in reactive oxygen species production in the mitochondrial inner membrane. We also review the current knowledge about the involvement of mitochondrial genome defects and electron transfer flavoprotein dehydrogenase mutations in the induction of secondary CoQ deficiency. This mechanism would imply specific interactions coupling CoQ itself or the CoQ-biosynthetic apparatus with the respiratory chain components. These interactions would regulate mitochondrial CoQ steady-state levels and function. 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.

Oxidative Phosphorylation System in Gastric Carcinomas and Gastritis

“…Also other proteins feed electrons into the respiratory chain like the mitochondrial sulfide:quinone oxidoreductase (SQRDL), the electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH), the glycerol-3-phosphate dehydrogenase (GPD2), and the sulfite oxidase (SUOX) that potentially contribute to residual respiration in complex I-negative tumors [56–59]. However, evidence that mitochondrial respiration is crucial for tumor cells comes from therapeutic studies, which, for example, show that inhibition of complex I and glucose restriction is lethal for cancer cells [60].…”

Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges

“…While an average healthy adult's body contains 0.5 to 1.5 g of CoQ10, its levels may be compromised by different factors (Bhagavan & Chopra, 2006). Deficiency can occur as a result of physiopathologic conditions such as acquired or genetic alterations in metabolism or biosynthesis (Alcázar-Fabra, Navas, & Brea-Calvo, 2016;Quinzii, DiMauro, & Hirano, 2007), an inadequate intake of CoQ10 or its dietary precursors (Potgieter et al, 2013), aging and oxidative stress that leads to an excessive utilization of the molecule (Nagase, Yamamoto, Matsumoto, Arai, & Hirose, 2018), or due to a combination of these factors. A suboptimal CoQ10 intake led to deficiencies when certain conditions or drugs were present.…”

“…Statins can also reduce CoQ10 concentration, since as HMG-CoA reductase inhibitors inhibit the production of mevalonate, which is not only a precursor of cholesterol but also of CoQ10 (Nawarskas, 2005). It has to be noted that CoQ10 endogenous synthesis is a complex process that requires the participation of tyrosine and eight vitamins (Alcázar-Fabra et al, 2016), which results in a high vulnerability of the process. Several signs, symptoms, and diseases have been associated to a significant depletion of CoQ10 levels.…”

Green Formulation of Triglyceride/Phospholipid‐Based Nanocarriers as a Novel Vehicle for Oral Coenzyme Q10 Delivery

“…Coenzyme Q10 (CoQ10, 2,3‐dimethoxy‐5‐methyl‐6‐decaprenyl‐1,4‐benzoquinone) is a lipophilic vitamin analog, present in all cells of human origin (Alcazar‐Fabra, Navas, & Brea‐Calvo, ). It scavenges free radicals, restrains lipid peroxidation and functions as a coenzyme in various metabolic pathways (Potgieter, Pretorius, & Pepper, ).…”