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

The mitochondrial genome encodes just a small number of subunits of the respiratory chain. All the other mitochondrial proteins are encoded in the nucleus and produced in the cytosol. Various enzymes participate in the activation and intra mitochondrial transport of imported proteins. To finally take their place in the various mitochondrial compartments, the targeting signals of imported proteins have to be cleaved by mitochondrial processing peptidases.

Mitochondrial aconitase is sensitive to oxidative inactivation and can aggregate and accumulate in various age-related disorders. We now report that the ATP-stimulated, mitochondrial-matrix, "Lon" protease selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification but severe oxidation results in aconitase aggregation, which makes it a poor Lon substrate. Similarly, a morpholino oligodeoxynucleotide