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PMID:12198491
| Citation |
Bota, DA and Davies, KJ (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat. Cell Biol. 4:674-80 |
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| Abstract |
Mitochondrial aconitase is sensitive to oxidative inactivation and can aggregate and accumulate in many age-related disorders. Here we report that Lon protease, an ATP-stimulated mitochondrial matrix protein, selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification, but that severe oxidation results in aconitase aggregation, which makes it a poor substrate for Lon. Similarly, a morpholino oligodeoxynucleotide directed against the lon gene markedly decreases the amount of Lon protein, Lon activity and aconitase degradation in WI-38 VA-13 human lung fibroblasts and causes accumulation of oxidatively modified aconitase. The ATP-stimulated Lon protease may be an essential defence against the stress of life in an oxygen environment. By recognizing minor oxidative changes to protein structure and rapidly degrading the mildly modified protein, Lon protease may prevent extensive oxidation, aggregation and accumulation of aconitase, which could otherwise compromise mitochondrial function and cellular viability. Aconitase is probably only one of many mitochondrial matrix proteins that are preferentially degraded by Lon protease after oxidative modification. |
| Links |
PubMed Online version:10.1038/ncb836 |
| Keywords |
ATP-Dependent Proteases; Aconitate Hydratase/chemistry; Aconitate Hydratase/metabolism; Adenosine Triphosphate/metabolism; Animals; Base Sequence; Cattle; Cell Line; Heat-Shock Proteins/antagonists & inhibitors; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Humans; Hydrogen Peroxide/pharmacology; Kinetics; Mitochondria/metabolism; Mitochondria, Heart/drug effects; Mitochondria, Heart/metabolism; Oligodeoxyribonucleotides, Antisense/genetics; Oligodeoxyribonucleotides, Antisense/pharmacology; Oxidation-Reduction; Serine Endopeptidases/genetics; Serine Endopeptidases/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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