title: High efficiency versus maximal performance--the cause of oxidative stress in eukaryotes: a hypothesis.
abstract: Degenerative diseases are in part based on elevated production of ROS (reactive oxygen species) in mitochondria, mainly during stress and excessive work under stress (strenuous exercise). The production of ROS increases with increasing mitochondrial membrane potential (ΔΨ(m)). A mechanism is described which is suggested to keep ΔΨ(m) at low values under normal conditions thus preventing ROS formation, but is switched off under stress and excessive work to maximize the rate of ATP synthesis, accompanied by decreased efficiency. Low ΔΨ(m) and low ROS production are suggested to occur by inhibition of respiration at high [ATP]/[ADP] ratios. The nucleotides interact with phosphorylated cytochrome c oxidase (COX), representing the step with the highest flux-control coefficient of mitochondrial respiration. At stress and excessive work neural signals are suggested to dephosphorylate the enzyme and abolish the control of COX activity (respiration) by the [ATP]/[ADP] ratio with consequent increase of ΔΨ(m) and ROS production. The control of COX by the [ATP]/[ADP] ratio, in addition, is proposed to increase the efficiency of ATP production via a third proton pumping pathway, identified in eukaryotic but not in prokaryotic COX. We conclude that 'oxidative stress' occurs when the control of COX activity by the [ATP]/[ADP] ratio is switched off via neural signals.
authors.affiliation: Department of Chemistry, Philipps-University, D-35032 Marburg, Germany. kadenbach@staff.uni-marburg.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kadenbach
authors.forename: Rabia
authors.initials: R
authors.lastname: Ramzan
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004734:Energy Metabolism; D056890:Eukaryota / Q000502:physiology*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate