Electron Transfer Mechanisms in Cytochrome bc1 Complex Systems

The cytochrome bc1 complex (Complex III) is a pivotal component of cellular respiration and photosynthesis, catalysing the transfer of electrons from ubiquinol to cytochrome c while concomitantly contributing to the proton motive force across biological membranes. Central to its catalytic cycle is the Mitchellian Q cycle, whereby sequential two-electron oxidation and reduction events at the quinol oxidation (Qo) and quinone reduction (Qi) sites drive proton translocation. The complex comprises three core subunits—cytochrome b, cytochrome c1 and the Rieske iron-sulfur protein—arranged as a dimer, often supplemented by additional supernumerary polypeptides in mitochondria. Electron bifurcation at the Qo site directs one electron through the high-potential Rieske cluster to cytochrome c1 and onward to soluble cytochrome c, while the second electron travels via haem bL and haem bH to the Qi site to regenerate quinol. Conformational dynamics of the Rieske domain and lipid interactions modulate quinone binding and redox coupling. Recent advances in structural biology, computational chemistry and biophysical methods have shed light on proton-electron coupling, transient semiquinone intermediates and supercomplex assembly, with profound implications for bioenergetics and drug discovery.

Research from Nature Portfolio

Structural elucidation of a bacterial bc1–cbb3 respiratory supercomplex at near-atomic resolution has revealed how membrane-confined electron carriers integrate with external cytochromes to optimise inter-complex communication. The work describes an active CIII2CIV assembly featuring mobile cyt cy domains that shuttle electrons from the bc1 core to the cbb3 oxidase by a pathway distinct from soluble cytochrome c2. Two additional transmembrane helices were identified as assembly factors stabilising the supercomplex. Functional assays demonstrated that this engineered complex retains full catalytic competence in vitro and in vivo, highlighting the architectural principles that govern supercomplex formation and electron flux in Gram-negative bacteria. These insights delineate parallel electron transfer pathways and provide a template for understanding respiratory chain organisation in diverse organisms.

Electron Transfer Mechanisms in Cytochrome bc1 Complex Systems publication trend

The graph below shows the total number of articles in electron transfer mechanisms in cytochrome bc1 complex systems across all publications each year (not limited to Nature Index journals).

Technical terms

Q cycle: The mechanism by which Complex III couples two-electron redox chemistry at quinone sites to proton translocation, generating proton motive force.

Quinol oxidation (Qo) site: The binding location in cytochrome bc1 where ubiquinol is oxidised, initiating electron bifurcation.

Quinone reduction (Qi) site: The site where ubiquinone is reduced to quinol, completing the Q cycle.

Rieske iron-sulfur protein: A subunit containing a [2Fe-2S] cluster that accepts one electron from ubiquinol at the Qo site and donates it to cytochrome c1.

Supercomplex: A stable assembly of respiratory or photosynthetic complexes, facilitating substrate channeling and enhancing catalytic efficiency.

References

1. Cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscs. Proceedings of the National Academy of Sciences of the United States of America (2023).
2. Cryo-EM structures of engineered active bc1-cbb3 type CIII2CIV super-complexes and electronic communication between the complexes. Nature Communications (2021).
3. Quinone binding sites of cyt bc complexes analysed by X-ray crystallography and cryogenic electron microscopy. Biochemical Society Transactions (2022).
4. Triplet State of the Semiquinone–Rieske Cluster as an Intermediate of Electronic Bifurcation Catalyzed by Cytochrome bc 1. Biochemistry (2013).