(A) In aerobic metabolism, ubiquinone (UQ) shuttles electrons in the ETC from Complex I (CI; yellow box) and quinone-coupled dehydrogenases (QDHs), such as Complex II. These electrons are ultimately transferred to oxygen. In anaerobic metabolism, rhodoquinone (RQ) reverses electron flow in QDHs and facilitates an early exit of electrons from the ETC onto anaerobic electron acceptors (Ae-A), such as fumarate. (B) The RQ biosynthetic pathway in C. elegans requires L-tryptophan, a precursor in the kynurenine pathway. L-Trptophan is transformed into 3-hydroxyanthranilic acid (3HA) in four steps. It is proposed that 3HA is a substrate for COQ-2, producing 3-hydroxy-5-nonaprenylanthranilic acid (NHA), where n=9. The transformation of NHA to RQ requires several shared proteins from the UQ biosynthetic pathway. (C) Eukaryotes can use either p-aminobenzoic acid (pABA) or 4-hydroxybenzoic acid (4HB) as precursors to UQ. Prenylation is facilitated by Coq2 to form 3-hexaprenyl-4-hydroxybenzoic acid (HHB) or 3-hexaprenyl-4-aminobenzoic acid (HAB), where n = varies between species. Further functionalization of these intermediates occurs through a Coq synthome (Coq3–Coq9 and Coq11) to yield UQ.