Linked Life Data

16617125

Source:http://linkedlifedata.com/resource/pubmed/id/16617125

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-8-10
pubmed:abstractText
Reactive oxygen species (ROS) play important roles in regulating mitochondrial function, as well as in ischemia-reperfusion injury and cardioprotection. Here we show that, in the absence of exogenous substrates, cardiac mitochondria have a surprisingly large capacity to phosphorylate ADP by oxidizing endogenous substrates, provided that H2O2 is removed from the extramitochondrial environment and a reduced environment is maintained in the matrix. In isolated mitochondria without exogenous substrates, addition of catalase and the membrane-permeant reducing agent N-acetylcysteine (Nac) or the ROS scavenger mercaptopropionyl glycine significantly increased the ability to phosphorylate added ADP, as demonstrated by 1) full recovery of membrane potential (Deltapsi) and matrix volume from ADP-induced dissipation and shrinkage, 2) ADP-dependent increase in O2 consumption, and 3) enhanced rate of ATP synthesis. Removal of extramitochondrial H2O2 by catalase was required to stimulate endogenous substrate oxidation, as shown by the increase in O2 consumption and Deltapsi. This effect was greatly enhanced by addition of Nac or mercaptopropionyl glycine to suppress oxidation-induced ROS increases in the matrix. Theoretical considerations, as well as reversible inhibition of O2 consumption with 3-mercaptopropionic acid and pyruvate in state 3, indicate that these substrates are fatty acids. Under in vivo conditions in which powerful antioxidant conditions are maintained, this mechanism may be important in stimulation of beta-oxidation and ATP production at low levels of extramitochondrial fatty acids. Incapacitation of this mechanism may potentially contribute to mitochondrial dysfunction during oxidative stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1436-45
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16617125-3-Mercaptopropionic Acid, pubmed-meshheading:16617125-Acetylcysteine, pubmed-meshheading:16617125-Adenosine Diphosphate, pubmed-meshheading:16617125-Adenosine Triphosphate, pubmed-meshheading:16617125-Animals, pubmed-meshheading:16617125-Catalase, pubmed-meshheading:16617125-Cell Respiration, pubmed-meshheading:16617125-Electron Transport, pubmed-meshheading:16617125-Enzyme Inhibitors, pubmed-meshheading:16617125-Fatty Acids, pubmed-meshheading:16617125-Hydrogen Peroxide, pubmed-meshheading:16617125-Mitochondria, Heart, pubmed-meshheading:16617125-Oxidants, pubmed-meshheading:16617125-Oxidation-Reduction, pubmed-meshheading:16617125-Oxidative Stress, pubmed-meshheading:16617125-Oxygen Consumption, pubmed-meshheading:16617125-Phosphorylation, pubmed-meshheading:16617125-Rabbits, pubmed-meshheading:16617125-Reactive Oxygen Species, pubmed-meshheading:16617125-Tiopronin
pubmed:year
2006
pubmed:articleTitle
Redox regulation of endogenous substrate oxidation by cardiac mitochondria.
pubmed:affiliation
Cardiovascular Research Laboratory, Department of Medicine, David Geffen University of California Los Angeles, School of Medicine, 3641 MRL Bldg., Los Angeles, CA 90095, USA. pkorge@mednet.ucla.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural