4.2.1. Mutations in Complex III Catalytic Subunits

Most of the known Complex III associated pathologies result from mutations in *MT-CYB*, the human mitochondrial cytochrome *b* gene, that have so far been described in 49 different positions of the genome [69]. Typical phenotypes include MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), LHON (Leber's Hereditary Optic Neuropathy), hearing loss and in some cases less severe phenotypes expressed in exercise intolerance (reviewed in [70]). While some cytochrome *b* mutations are maternally inherited, others are heteroplasmic and are present mainly in muscle tissue, suggesting that they arise de novo after differentiation of the primary germ layers. Additionally, some LHON patients with a mutation in one of the mitochondrially encoded Complex I genes have a second mutation in cytochrome *b*, which exacerbates the severity of the pathology [71–73]. Mutations in the nuclear *UQCR4* (yeast *CYC1*) and *UQCRFS1* (yeast *RIP1*) genes are much rarer and were more recently identified (Table 3).
