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COA8 is a COX10-binding protein involved in the early biogenesis of cytochrome c oxidase

Fernandez-Vizarra, E.; Brischigliaro, M.; Cunatova, K.; Cabrera-Orefice, A.; Pei, J.; Franchin, C.; Roverso, M.; Povea-Cabello, S.; Bogialli, S.; Arrigoni, G.; Arnold, S.; Cong, Q.; Zeviani, M.; Viscomi, C.

2024-04-02 biochemistry
10.1101/2024.04.02.587738 bioRxiv
Show abstract

Human cytochrome c oxidase (COX) is composed of fourteen subunits, only two of which are catalytic. The functions of a myriad of accessory factors are needed to put together the structural subunits, as well as for the formation of the active centers. The molecular roles of most of these factors are still unknown, even if they are essential for COX function since their defects cause severe mitochondrial disease. COA8 is exclusively found in metazoa and loss-of-function genetic variants cause mitochondrial encephalopathy and COX deficiency in humans. In this work, we have resolved the function of COA8, as a factor that specifically binds to COX10, the heme O synthase. This interaction is necessary not only for the stabilization of human COX10, but also to guarantee its catalytic activity as the first step for the synthesis of the heme A cofactor, which is a crucial component of the COX catalytic center.

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