Hartmut Michel

Energy Conversion in Cellular Respiration

Tuesday, 26 June 2001
13:40 - 14:10 hrs CEST

Abstract

Animals, and most fungi and bacteria, obtain their energy by “burning“ foodstuff. This happens stepwise in a very controlled manner. The foodstuff (carbohydrates, fats) is first degraded and biologically fixed hydrogen is generated in the form of NADH. NADH is then oxidized in the so-called respiratory chain, which is located in the inner membrane of mitochondria and bacteria. The respiratory chain consists of complex I (NADH-ubiquinone oxidoreductase), complex II (succinate dehydrogenase), complex III (ubiquinol cytochrome c oxidoreductase or cytochrome bc1 complex) and complex IV (cytochrome c oxidase). Complexes I, III and IV are “proton pumps“, this means that they translocate protons across the membrane. This process leads to the generation of an electric field and a pH-gradient across the membrane. Protons flow back via the ATP-synthase, where they drive the synthesis of ATP, the universal energy currency of life.

We have crystallized the cytochrome bc1 complex and cytochrome c oxidase, and determined their structures in order to have a basis to understand the mechanism of proton pumping. The structures of both complexes will be described. Whereas the mechanism of proton pumping by the cytochrome bc1 complex appears to be understood (quinols diffuse across the membrane, protons are realized to the outside, and 50% of the electrons are shuttled back), the mechanism of proton pumping by cytochrome c oxidase is highly controversial. Cytochrome c oxidase is the terminal enzyme of the respiratory chain, it uses four electrons (from cytochrome c), four protons and one molecule of dioxygen to generate two molecules of water and to pump four protons. Even the question which of the four electron transfers are coupled to proton pumping is under debate. Recent experiments to clarify this issue will also be presented.

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