Control of transmembrane charge transfer in cytochrome c oxidase by the membrane potential

• Published in: Nature communications 2018-08, Vol.9 (1), p.3187-8, Article 3187
• Main Authors: Björck, Markus L., Brzezinski, Peter
• Format: Article
• Language: English
• Subjects: 631/45/173; 631/45/49/1140; 631/45/49/1141; 631/45/49/1142; 631/57/1464; Adenosine Triphosphate - chemistry; Animals; Biochemistry; biokemi; Catalysis; Catalytic Domain; Cattle; Charge transfer; Chemical reactions; Cytochrome; Cytochrome-c oxidase; Cytochromes; Electrochemical potential; Electrochemistry; Electron transfer; Electron Transport; Electron Transport Complex IV - metabolism; Electrons; Humanities and Social Sciences; Hydrogen-Ion Concentration; Hydrolysis; Ion Transport; Membrane potential; Membrane Potential, Mitochondrial; Membranes; Mitochondria; Mitochondria - metabolism; Mitochondrial DNA; Mitochondrial Membranes - metabolism; multidisciplinary; Myocardium - metabolism; Oxidase; Oxygen - chemistry; Proteins; Proton Pumps - metabolism; Protons; Science; Science (multidisciplinary); Translocation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05615-5

The respiratory chain in mitochondria is composed of membrane-bound proteins that couple electron transfer to proton translocation across the inner membrane. These charge-transfer reactions are regulated by the proton electrochemical gradient that is generated and maintained by the transmembrane charge transfer. Here, we investigate this feedback mechanism in cytochrome c oxidase in intact inner mitochondrial membranes upon generation of an electrochemical potential by hydrolysis of ATP. The data indicate that a reaction step that involves proton uptake to the catalytic site and presumably proton translocation is impaired by the potential, but electron transfer is not affected. These results define the order of electron and proton-transfer reactions and suggest that the proton pump is regulated by the transmembrane electrochemical gradient through control of internal proton transfer rather than by control of electron transfer. Cytochrome c oxidase (Cyt c O) is the last enzyme of the electron transport chain, but how the electrochemical membrane potential affects Cyt c O is unclear. Here the authors show that proton uptake to the catalytic site of Cyt c O and presumably proton translocation was impaired by the potential, but electron transfer was not affected.