title: Degenerative diseases, oxidative stress and cytochrome c oxidase function.
abstract: Aging and degenerative diseases are associated with increased levels of reactive oxygen species (ROS). ROS are mostly produced in mitochondria, and their levels increase with higher mitochondrial membrane potential. Cellular respiratory control is based on inhibition of respiration by high membrane potentials. However, we have described a second mechanism of respiratory control based on allosteric inhibition of cytochrome c oxidase (CcO), the terminal enzyme of the respiratory chain, at high ATP:ADP ratios. The mechanism is independent of membrane potential. We have proposed that feedback inhibition of CcO by ATP keeps the membrane potential and ROS production at low levels. Various forms of stress switch off allosteric ATP-inhibition via reversible dephosphorylation of CcO, resulting in increased membrane potential and cellular ROS levels. This mechanism is proposed to represent a missing molecular link between stress and degenerative diseases.
authors.affiliation: Fachbereich Chemie, 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; D000818:Animals; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV