Aconitase and ATP synthase are targets of malondialdehyde modification and undergo an age-related decrease in activity in mouse heart mitochondria.
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.
Yarian
Connie S
CS
Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Rebrin
Igor
I
Sohal
Rajindar S
RS
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*
D008315:Malondialdehyde; D025261:Mitochondrial Proton-Translocating ATPases; D000154:Aconitate Hydratase