The cytochrome b carboxyl terminal region is necessary for mitochondrial complex III assembly.

Flores-Mireles D; Camacho-Villasana Y; Lutikurti M; Garcia-Guerrero AE; Lozano-Rosas G; Chagoya V; Gutierrez-Cirlos EB; Brandt U; Cabrera-Orefice A; Perez-Martinez X (2023). The cytochrome b carboxyl terminal region is necessary for mitochondrial complex III assembly. Life Sci Alliance 6

ABSTRACT

Mitochondrial bc 1 complex from yeast has 10 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. Because 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 because of the absence of fully assembled bc 1 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 bc 1 complex assembly.



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