Effects of mtDNA variants on OXPHOS complex stability, assembly, and activity. A mtDNA variant can affect OXPHOS complex function at each stage of OXPHOS complex translation and assembly (illustrated using complex I but applicable for the other OXPHOS complexes). mtDNA variants can reduce the stability of mRNA, complex subunits, fully assembled complexes, or supercomplexes. mtDNA variants can hinder assembly of the OXPHOS complex or supercomplexes or prevent post-translational modifications. Additionally, mtDNA variants can alter the ratio of OXPHOS complexes forming a supercomplex. Ultimately, mtDNA variants can result in a loss of one or more OXPHOS complexes or induce a change in the kinetic activity of the affected complex, shown as a change in Michaelis–Menten kinetics of the affected enzyme. A higher Km for the affected complex I (Km2) compared with the normal complex I (Km1) indicates a decrease in affinity for a substrate.
