PMID- 19303362
OWN - NLM
STAT- MEDLINE
DCOM- 20090623
LR  - 20131121
IS  - 1471-4914 (Print)
IS  - 1471-4914 (Linking)
VI  - 15
IP  - 4
DP  - 2009 Apr
TI  - Degenerative diseases, oxidative stress and cytochrome c oxidase function.
PG  - 139-47
LID - 10.1016/j.molmed.2009.02.004 [doi]
AB  - 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.
FAU - Kadenbach, Bernhard
AU  - Kadenbach B
AD  - Fachbereich Chemie, Philipps-University, D-35032 Marburg, Germany. 
      Kadenbach@staff.uni-marburg.de
FAU - Ramzan, Rabia
AU  - Ramzan R
FAU - Vogt, Sebastian
AU  - Vogt S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090318
PL  - England
TA  - Trends Mol Med
JT  - Trends in molecular medicine
JID - 100966035
RN  - 0 (Reactive Oxygen Species)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Electron Transport Complex IV/chemistry/genetics/*metabolism
MH  - Humans
MH  - Membrane Potential, Mitochondrial/physiology
MH  - Mitochondrial Diseases/genetics/metabolism
MH  - Models, Biological
MH  - Oxidative Stress/*physiology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2009/03/24 09:00
MHDA- 2009/06/24 09:00
CRDT- 2009/03/24 09:00
PHST- 2008/12/11 00:00 [received]
PHST- 2009/02/02 00:00 [revised]
PHST- 2009/02/05 00:00 [accepted]
PHST- 2009/03/24 09:00 [entrez]
PHST- 2009/03/24 09:00 [pubmed]
PHST- 2009/06/24 09:00 [medline]
AID - S1471-4914(09)00046-X [pii]
AID - 10.1016/j.molmed.2009.02.004 [doi]
PST - ppublish
SO  - Trends Mol Med. 2009 Apr;15(4):139-47. doi: 10.1016/j.molmed.2009.02.004. Epub 
      2009 Mar 18.