The cytochrome b carboxyl-terminal region is necessary for mitochondrial Complex III assembly

Flores-Mireles, D.; Camacho-Villasana, Y.; Lutikurti, M.; Garcia-Guerrero, A. E.; Lozano-Rosas, G.; Chagoya, V.; Gutierrez-Cirlos, E. B.; Brandt, U.; Cabrera-Orefice, A.; Perez-Martinez, X.

doi:10.1101/2022.11.25.517933

bioRxiv · 10.1101/2022.11.25.517933

The cytochrome b carboxyl-terminal region is necessary for mitochondrial Complex III assembly

Flores-Mireles, D.·Camacho-Villasana, Y.·Lutikurti, M.·Garcia-Guerrero, A. E.·Lozano-Rosas, G.·Chagoya, V.·Gutierrez-Cirlos, E. B.·Brandt, U.·Cabrera-Orefice, A.·Perez-Martinez, X.

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Abstract

Mitochondrial bc1 complex from yeast has ten subunits, but only Cytochrome b (Cytb) subunit is encoded in the mitochondrial genome. Cytb has eight transmembrane helices containing two hemes b for electron transfer. Cbp3 and Cbp6 assist Cytb synthesis, and together with Cbp4 induce Cytb hemylation. Subunits Qcr7/Qcr8 participate in the first steps of assembly, and lack of Qcr7 reduces Cytb synthesis through an assembly-feedback mechanism involving Cbp3/Cbp6. Since Qcr7 resides near the Cytb carboxyl-region, we wondered whether this region is important for Cytb synthesis/assembly. Although deletion of the Cytb C-region did not abrogate Cytb synthesis, the assembly-feedback regulation was lost, so Cytb synthesis was normal even if Qcr7 was missing. Mutants lacking the Cytb C-terminus were non-respiratory due to absence of fully assembled bc1 complex. By performing complexome profiling, we showed the existence of aberrant early-stage subassemblies in the mutant. In this work we demonstrate that the C-terminal region of Cytb is critical for regulation of Cytb synthesis and bc1 complex assembly.

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Flores-Mireles, D., Camacho-Villasana, Y., Lutikurti, M., Garcia-Guerrero, A. E., Lozano-Rosas, G., Chagoya, V., Gutierrez-Cirlos, E. B., Brandt, U., Cabrera-Orefice, A., Perez-Martinez, X.. 2022-11-27. The cytochrome b carboxyl-terminal region is necessary for mitochondrial Complex III assembly. https://doi.org/10.1101/2022.11.25.517933

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