Similar Transition States Mediate the Q-cycle and Superoxide Production by the Cytochrome bc1 Complex

Journal Article · Fri Dec 15 04:00:00 EST 2006 · Journal of Biological Chemistry, 281(50):38459-38465

DOI:https://doi.org/10.1074/jbc.M605119200· OSTI ID:897679

Forquer, Isaac P; Covian, Raul; Bowman, Michael K; Trumpower, Bernard; Kramer, David M

The cytochrome bc complexes found in mitochondria, chloroplasts and many bacteria catalyze a critical reaction in their respective electron transport chains. The quinol oxidase (Qo) site in this complex oxidizes a hydroquinone (quinol), reducing two one-electron carriers, a low-potential cytochrome b heme and a ''Rieske'' iron-sulfur cluster. The overall electron transfer reactions are coupled to transmembrane translocation of protons via a ''Q-cycle'' mechanism, which generates proton motive force for ATP synthesis. Since semiquinone intermediates of quinol oxidation are generally highly reactive, one of the key questions in this field is: how does the Qo site oxidize quinol without the production of deleterious side reactions including superoxide production? We attempt to test three possible general models to account for this behavior: (1) The Qo site semiquinone (or quinol:imidazolate complex) is unstable and thus occurs at a very low steady-state concentration, limiting O2 reduction; (2) the Qo site semiquinone is highly stabilized making it unreactive towards oxygen; and (3) the Qo site catalyzes a quantum mechanically-coupled two-electron/two proton transfer without a semiquinone intermediate. Enthalpies of activation were found to be almost identical between the uninhibited Q-cycle and superoxide production in the presence of Antimycin A in wild type. This behavior was also preserved in a series of mutants with altered driving forces for quinol oxidation. Overall, the data supports models where the rate-limiting step for both Q-cycle and superoxide production are essentially identical, consistent with model 1 but requiring modifications to models 2 and 3.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 897679
• Report Number(s): PNWD-SA-7426; 19832
• Journal Information: Journal of Biological Chemistry, 281(50):38459-38465, Journal Name: Journal of Biological Chemistry, 281(50):38459-38465
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS
ANTIBIOTICS
BACTERIA
CHLOROPLASTS
CYTOCHROMES
ELECTRON TRANSFER
ELECTRONS
Environmental Molecular Sciences Laboratory
HEME
MITOCHONDRIA
MODIFICATIONS
MUTANTS
OXIDASES
OXIDATION
OXYGEN
PROTONS
SYNTHESIS
TRANSLOCATION