New control of mitochondrial membrane potential and ROS formation--a hypothesis.
A new control of mitochondrial membrane potential delta(psi)m and formation of reactive oxygen species (ROS) is presented, based on allosteric ATP-inhibition 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 delta(psi)m (at constant rate of ATP consumption). Therefore the control of respiration by the ATP/ADP-ratio keeps delta(psi)m low. In contrast, the known 'respiratory control' leads to an inhibition of respiration only at high delta(psi)m values (150-200 mV) which cause ROS formation. ATP-inhibition 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 [Ca2+] also increase delta(psi)m and ROS formation, which promote degenerative diseases and accelerate aging.
Lee
I
I
Fachbereich Chemie, Philipps-Universität, Marburg, Germany.
Bender
E
E
Arnold
S
S
Kadenbach
B
B
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D000494:Allosteric Regulation / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D019069:Cell Respiration / Q000502:physiology; D016384:Consensus Sequence; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV