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Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic Membranes

Journal

CHEMICAL REVIEWS
Volume 121, Issue 15, Pages 9644-9673

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrev.1c00140

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Funding

  1. Knut and Wallenberg Foundation [2019.0043]
  2. Swedish Research Council [201804619]
  3. National Institutes of Health [R01-GM129325]
  4. Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases

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In aerobic organisms, the free energy from electron transfer in the respiratory chain is converted into a proton electrochemical gradient across the membrane for energy storage. Cytochrome c oxidase and cytochrome bc1 combine to form supercomplexes in many organisms, facilitating energy conversion through complex mechanisms and structures.
In the final steps of energy conservation in aerobic organisms, free energy from electron transfer through the respiratory chain is transduced into a proton electrochemical gradient across a membrane. In mitochondria and many bacteria, reduction of the dioxygen electron acceptor is catalyzed by cytochrome c oxidase (complex IV), which receives electrons from cytochrome bc(1) (complex III), via membrane-bound or watersoluble cytochrome c. These complexes function independently, but in many organisms they associate to form supercomplexes. Here, we review the structural features and the functional significance of the nonobligate III2IV1/2 Saccharomyces cerevisiae mitochondrial super-complex as well as the obligate III2IV2 supercomplex from actinobacteria. The analysis is centered around the Q-cycle of complex III, proton uptake by CytcO, as well as mechanistic and structural solutions to the electronic link between complexes III and IV.

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