4.6 Article

Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart

期刊

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 490, 期 1, 页码 30-35

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.08.002

关键词

Aging; Rat heart mitochondria; Electron transport supercomplexes; Blue native-polyacrylamide gel electrophoresis

资金

  1. National Institute on Aging [2R01AG017141-06A2, R01AG025372]
  2. National Institutes of Health
  3. National Institute of Environmental Health Sciences at Oregon State University [P30ES00210]

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Accumulation of mitochondrial electron transport chain (ETC) defects is a recognized hallmark of the age-associated decline in cardiac bioenergetics; however, the molecular events involved are only poorly understood. In the present work, we hypothesized that age-related ETC deterioration stemmed partly from disassociation of large solid-state macromolecular assemblies termed supercomplexes. Mitochondrial proteins from young and old rat hearts were separated by blue native-PAGE, protein bands analyzed by LC-MALDI-MS/MS, and protein levels quantified by densitometry. Results showed that supercomplexes comprised of various stoichiometries of complexes I, III and IV were observed, and declined significantly (p < 0.05, n = 4) with age. Supercomplexes displaying the highest molecular masses were the most severely affected. Considering that certain diseases (e.g. Barth Syndrome) display similar supercomplex destabilization as our results for aging, the deterioration in ETC supercomplexes may be an important underlying factor for both impaired mitochondrial function and loss of cardiac bioenergetics with age. (C) 2009 Elsevier Inc. All rights reserved.

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