title: Aconitase and ATP synthase are targets of malondialdehyde modification and undergo an age-related decrease in activity in mouse heart mitochondria.
abstract: The main purpose of this study was to identify mitochondrial proteins that exhibit post-translational oxidative modifications during the aging process and to determine the resulting functional alterations. Proteins forming adducts with malondialdehyde (MDA), a product of lipid peroxidation, were identified by immunodetection in mitochondria isolated from heart and hind leg skeletal muscle of 6-, 16-, and 24-month-old mice. Aconitase, very long chain acyl coenzyme A dehydrogenase, ATP synthase, and alpha-ketoglutarate dehydrogenase were detected as putative targets of oxidative modification by MDA. Aconitase and ATP synthase from heart exhibited significant decreases in activity with age. Very long chain acyl coenzyme A dehydrogenase and alpha-ketoglutarate dehydrogenase activities were unaffected during aging in both heart and skeletal muscle. This suggests that the presence of a post-translational oxidative modification in a protein does not a priori reflect an alteration in activity. The biological consequences of an age-related decrease in aconitase and ATP synthase activities may contribute to the decline in mitochondrial bioenergetics evident during aging.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Yarian
authors.forename: Igor
authors.initials: I
authors.lastname: Rebrin
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D008315:Malondialdehyde; D025261:Mitochondrial Proton-Translocating ATPases; D000154:Aconitate Hydratase