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Icksoo Lee, Elisabeth Bender, Susanne Arnold, Bernhard Kadenbach

New Control of Mitochondrial Membrane Potential and ROS Formation A Hypothesis

A new control of mitochondrial membrane potential ??m and formation of reactive oxygen species (ROS) is presented, based on allosteric ATPinhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP ratios. Since the rate of ATP synthesis by the ATP synthase is already maximal at low membrane potentials (100 120 mV), the ATP/ADP ratio will also be maximal at this ??m (at constant rate of ATP consumption). Therefore the control of respiration by the ATP/ADPratio keeps ??m low. In contrast, the known respiratory control leads to an inhibition of respiration only at high ??m values (150 200 mV) which cause ROS formation. ATPinhibition of cytochrome c oxidase is switched on and off by reversible phosphorylation (via cAMP and calcium, respectively). We propose that stress hormones which increase intracellular [Ca 2+ ] also increase ??m and ROS formation, which promote degenerative diseases and accelerate aging.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 382, 12/2001
Pages: 1629 - 1633

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