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Conformational changes in cytochromeaa 3 and ATP synthetase of the mitochondrial membrane and their role in mitochondrial energy transduction

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Summary

  1. 1.

    The thermodynamics and molecular basis of energy-linked conformational changes in the cytochromeaa 3 and ATP synthetase complexes of the mitochondrial membrane have been studied with spectrophotometrical and fluorometrical techniques.

  2. 2.

    Ferric cytochromeaa 3 exists in two conformations, high spin and low spin, the equilibrium between these states being controlled by the electrical potential difference across the mitochondrial membrane. The conformational change is brought about by an electrical fielddriven binding of one proton peraa 3 to the complex. At pH 7.2 the concentration of the two conformations is equal at a membrane potential of 170 mV corresponding to about 4 kcal/mole.

  3. 3.

    The high to low spin transition in ferricaa 3 is also induced by hydrolysis of ATP in which case two molecules ofaa 3 are shifted per ATP molecule hydrolyzed. This is in accordance with translocation of two protons across the mitochondrial membrane coupled to hydrolysis of ATP as proposed in the chemiosmotic theory of oxidative phosphorylation.

  4. 4.

    The conformational transition in cytochromeaa 3 is not an expression of the formation of a ‘high-energy’ intermediate or reversal of the energy-transducing pathway of oxidative phosphorylation, but is presumably the basis of allosteric control of the activity of cytochrome oxidase by the energy state of the mitochondrion. This control is exerted by a regulatory mechanism in which the electrical potential difference controls the conformation and redox properties of the heme centres and thereby the rate of oxygen consumption.

  5. 5.

    The synthesis of one molecule of ATP by oxidative phosphorylation is energetically equivalent to the work done in carrying two electrical charges across the entire mitochondrial membrane.

  6. 6.

    Fluorescence changes of aurovertin bound to ATP synthetase reveal that the electrical membrane potential induces a conformational change in the F1 portion of the enzyme which is probably associated with dissociation of the natural F1 inhibitor protein. This conformational change is energetically equivalent to the work done in carrying one electrical charge across the mitochondrial membrane.

  7. 7.

    A model is proposed for the mechanism of the electrical field-induced conformational changes in the cytochromeaa 3 and ATP synthetase complexes, and the significance of these changes in the mechanism and control of mitochondrial energy conservation is discussed.

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  1. Department of Medical Chemistry, University of Helsinki, Siltavuorenpenger 10 A, 00170, Helsinki 17, Finland

    Mårten K. F. Wikström & Herkko T. Saari

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  1. Mårten K. F. Wikström
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This solicited article reviews recent progress in our studies on the mechanism of energy transduction in mitochondria.

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Wikström, M.K.F., Saari, H.T. Conformational changes in cytochromeaa 3 and ATP synthetase of the mitochondrial membrane and their role in mitochondrial energy transduction. Mol Cell Biochem 11, 17–33 (1976). https://doi.org/10.1007/BF01792831

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