Mitochondrial respiratory Complex III (cytochrome bc1) — subunits and assembly; UQCRC1/UQCRC2/UQCRB/UQCRQ/UQCRH/UQCRFS1/CYC1 + BCS1L/LYRM7/TTC19/UQCC2/UQCC3

Respiratory Complex III (ubiquinol-cytochrome c oxidoreductase, the cytochrome bc1 complex) is the central proton-pumping enzyme of the mitochondrial electron transport chain: it oxidises ubiquinol and reduces cytochrome c through the protonmotive Q cycle, contributing to the transmembrane proton gradient that drives ATP synthesis. The functional complex is a homodimer, each protomer built from cytochrome b (mtDNA-encoded MT-CYB) and ten nuclear-encoded subunits. The three redox centres reside in cytochrome b (the two b-hemes and the Qo/Qi ubiquinone sites), the Rieske iron-sulfur protein UQCRFS1 (the [2Fe-2S] cluster), and cytochrome c1 (CYC1); the hinge protein UQCRH mediates the cytochrome c1-cytochrome c electron-transfer interface. The two large "core proteins" UQCRC1 and UQCRC2 (peptidase-M16-fold but non-catalytic) and the small subunits UQCRB and UQCRQ are structural, providing the scaffold and the ubiquinone-binding environment. Assembly is stepwise and requires dedicated factors: UQCC2 (with UQCC1) stabilises and promotes translation of MT-CYB to nucleate the complex; UQCC3 stabilises the cytochrome-b assembly intermediate and (via cardiolipin binding) supports supercomplex organisation; LYRM7 is a matrix chaperone that holds apo-UQCRFS1 before [2Fe-2S] insertion; BCS1L is the AAA-ATPase translocase that inserts the matured Rieske protein into the nearly complete complex; and TTC19 clears the UQCRFS1 N-terminal fragments generated during Rieske maturation. Inherited defects in the subunits or assembly factors cause mitochondrial complex III deficiency (a spectrum of encephalopathy, leukoencephalopathy, lactic acidosis, tubulopathy and — for BCS1L — GRACILE syndrome).