Respiratory complexes are complicated multi-subunit cofactor-containing machines that allow cells to harvest energy from the environment. Maturation of these complexes requires protein folding, cofactor insertion, and assembly of multiple subunits into a final, functional complex. Because the intermediate states in complex maturation are transitory, these processes are poorly understood. This review gives an overview of the process of maturation in respiratory complex II with a focus on recent structural studies on intermediates formed during covalent flavinylation of the catalytic subunit, SDHA. Covalent flavinylation has an evolutionary significance because variants of complex II enzymes with the covalent ligand removed by mutagenesis cannot oxidize succinate, but can still perform the reverse reaction and reduce fumarate. Since succinate oxidation is a key step of aerobic respiration, the covalent bond of complex II appears to be important for aerobic life.
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