Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart.
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.
Gómez
Luis A
LA
Linus Pauling Institute and Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Monette
Jeffrey S
JS
Chavez
Juan D
JD
Maier
Claudia S
CS
Hagen
Tory M
TM
D000375:Aging; D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344
D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
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