Figure 2.

Causes of secondary CoQ deficiency. Mechanisms proposed to trigger the secondary variant are grouped in several categories (G1 to G6) indicated in different colors. The synthesis of CoQ can be reduced by defects in proteins implicated directly or indirectly in the assembly and proper respiratory machinery functioning (G1 (blue) and G3 (red)). In orange (G2) are the essential proteins for the maintenance of intact mtDNA. Point mutations in mitochondrial aminoacyl-tRNA synthetases are also associated with low CoQ levels. The stability of Q-synthome depends on ER-mitochondrial contact sites (ERMES) and the cholesterol synthesis pathway (G4 (purple)). Defects in the proteins implicated in the transport of several metabolites, such as glucose or Fe²⁺, throughout to plasm or mitochondrial membrane cause channelopathies, marked in green (G5). The mechanisms to maintain mitochondrial mass by processes such as fusion-fission proteins, MFN1, and MFN2 (G6) are shown in yellow.