Assembly of the Multi-Subunit Cytochrome bc1 Complex in the Yeast Saccharomyces cerevisiae

Abstract

The cytochrome bc₁ complex is an essential component of the mitochondrial respiratory chain of the yeast Saccharomyces cerevisiae. It is composed of ten protein subunits, three of them playing an important role in electron transfer and proton pumping across the inner mitochondrial membrane. Cytochrome b, the central component of this respiratory complex, is encoded by the mitochondrial genome, whereas all the other subunits are of nuclear origin. The assembly of all these subunits into the mature and functional cytochrome bc₁ complex is therefore a complicated process which requires the participation of several chaperone proteins. It has been found that the assembly process of the mitochondrial bc₁ complex proceeds through the formation of distinct sub-complexes in an ordered sequence. Most of these sub-complexes have been thoroughly characterized, and their molecular compositions have also been defined. This study critically analyses the results obtained so far and highlights new possible areas of investigation.

Keywords: chaperones; complex III; mitochondria; mitochondrial biogenesis; respiratory chain; respiratory complexes; respiratory sub-complexes; respiratory super-complexes; yeast strains.

Figure 1

Location of the cytochrome bc₁ complex (or complex III) in the inner mitochondrial membrane of Saccharomyces cerevisiae as part of the mitochondrial respiratory chain. Complex III is shown in association with complex IV (respiratory super-complex).

Figure 2

Structure of the homodimeric bc₁ complex in the inner mitochondrial membrane based on the crystal structure analysis carried out in yeast mitochondria (cytochrome b: aquamarine, cytochrome c₁: yellow, ISP: green, core protein 1: light blue, core protein 2: salmon, Qcr6p: sky blue, Qcr7p: orange, Qcr8p: pink, Qcr9p: magenta).

Figure 3

Schematic model depicting the putative multi-step assembly of the mitochondrial bc₁ complex (cytochrome b: aquamarine, cytochrome c₁ (Cytc₁): yellow, ISP: green, core protein 1 (Core1p): light blue, core protein 2 (Core2p): salmon, Qcr6p: sky blue, Qcr7p: orange, Qcr8p: pink, Qcr9p: magenta). Cbp3p, Cbp4p and Cbp6p structures were obtained from the UniProt database (https://www.uniprot.org) (accessed on 24 August 2022) using the protein structure prediction tool AlphaFold. The interaction sites between chaperone proteins and bc₁ subunits remain unknown.

Figure 4

Different forms of the bc₁ late core identified in four yeast mutant strains: (a) Δqcr9; (b) Δisp; (c) Δbcs1; (d) Δqcr6/Δqcr9. The bc₁ late core is depicted in its monomeric form (cytochrome b: aquamarine, cytochrome c₁: yellow, core protein 1: light blue, core protein 2: salmon, Qcr6p: sky blue, Qcr7p: orange, Qcr8p: pink, Qcr9p: magenta). The Bcs1p structure was obtained from the UniProt database (https://www.uniprot.org) (accessed on 24 August 2022) using the protein structure prediction tool AlphaFold. The interaction sites between Bcs1p (protein coloured in green) and bc₁ late core subunits remain unknown.

Figure 5

Additional bc₁ sub-complexes. (a) Sub-complex containing cytochrome c₁ (yellow) and core protein 2 (salmon). (b) Sub-complex containing cytochrome c₁ and core protein 1 (light blue). (c) Sub-complex containing ISP (green) and Qcr9p (magenta). This figure shows the interaction between the indicated bc₁ subunits on the basis of the crystal structure analysis carried out in yeast mitochondria.