Title | Two subpopulations of mitochondria in the aging rat heart display heterogenous levels of oxidative stress. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Authors | Suh JH, Heath S-H, Hagen TM |
Journal | Free Radic Biol Med |
Volume | 35 |
Issue | 9 |
Pagination | 1064-72 |
Date Published | 2003 Nov 01 |
ISSN | 0891-5849 |
Keywords | Aging, Aldehydes, Animals, Antimycin A, Antioxidants, Electron Transport, Electron Transport Complex IV, Male, Mitochondria, Heart, Molecular Weight, Myocardium, Oxidants, Oxidation-Reduction, Oxidative Stress, Rats, Rats, Inbred F344, Sulfhydryl Compounds, Thioredoxins |
Abstract | Cardiac mitochondria are composed of two distinct subpopulations: one beneath the sarcolemma (subsarcolemmal mitochondria: SSM), and another along the myofilaments (interfibrillary mitochondria: IFM). Previous studies suggest a preferential loss of IFM function with age; however, the age-related changes in oxidative stress in these mitochondrial subpopulations have not been examined. To this end, the changes in mitochondrial antioxidant capacity, oxidant output, and oxidative damage to Complex IV in IFM and SSM from young and old rats were studied. Results show no apparent differences in any parameters examined between IFM and SSM from young rats. However, relative to young, only IFM from old rats had a significantly higher rate of oxidant production and a decline in mitochondrial ascorbate levels and GSH redox status. The age-related decline in mitochondrial antioxidant capacity in IFM was accompanied by a marked loss in glutaredoxin and GSSG reductase activities, suggesting a diminished reductive capacity in IFM with age. Moreover, the loss in Complex IV activity was limited to the IFM of old rats, which was accompanied by a 4-fold increase in 4-hydroxynonenal-modified Complex IV. Thus, mitochondrial decay is not uniform and further indicates that myofibrils may be uniquely under oxidative stress in the aging heart. |
Alternate Journal | Free Radic. Biol. Med. |
PubMed ID | 14572609 |
PubMed Central ID | PMC4696537 |
Grant List | R01 AG017141 / AG / NIA NIH HHS / United States RIAG17141A / AG / NIA NIH HHS / United States |