Modulation of Lon protease activity and aconitase turnover during aging and oxidative stress.
We compared Lon protease expression in murine skeletal muscle of young and old, wild-type and Sod2(-/+) heterozygous mice, and studied Lon involvement in the accumulation of damaged (oxidized) proteins. Lon protease protein levels were lower in old and oxidatively challenged animals, and this Lon deficiency was associated with increased levels of carbonylated proteins. We identified one of these proteins as aconitase, and another as an aconitase fragmentation product, which we can also generate in vitro by treating purified aconitase with H(2)O(2). These results imply that aging and oxidative stress down-regulate Lon protease expression which, in turn, may be responsible for the accumulation of damaged proteins, such as aconitase, within mitochondria.
Bota
Daniela A
DA
Ethel Percy Andrus Gerontology Center, 3715 McClintock Avenue, University of Southern California, Los Angeles, CA 90089-0191, USA.
Van Remmen
Holly
H
Davies
Kelvin J A
KJ
D049069:ATP-Dependent Proteases; D000154:Aconitate Hydratase / Q000378:metabolism*; D000375:Aging; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology; D018384:Oxidative Stress; D012697:Serine Endopeptidases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D049069:ATP-Dependent Proteases; D000154:Aconitate Hydratase; D000447:Aldehydes; D006360:Heat-Shock Proteins; D012697:Serine Endopeptidases; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2