Oxidized mitochondrial protein degradation and repair in aging and oxidative stress.
Proteins are main targets for oxidative damage that occurs during aging and in oxidative stress situations. Since the mitochondria is a major source of reactive oxygen species, mitochondrial proteins are especially exposed to oxidative modification, and elimination of oxidized proteins is crucial for maintaining the integrity of this organelle. Hence, enzymatic reversal of protein oxidation and protein degradation is critical for protein homeostasis while protein maintenance failure has been implicated in the age-related accumulation of oxidized proteins. Within the mitochondrial matrix, the ATP-stimulated mitochondrial Lon protease is believed to play an important role in the degradation of oxidized protein, and age-associated impairment of Lon-like protease activity has been suggested to contribute to oxidized protein buildup in the mitochondria. Oxidized protein repair is limited to certain oxidation products of the sulfur-containing amino acids cysteine and methionine. Oxidized protein repair systems, thioredoxin/thioredoxin reductase or glutaredoxin/glutathione/glutathione reductase that catalytically reduce disulfide bridges or sulfenic acids, and methionine sulfoxide reductase that reverses methionine sulfoxide back to methionine within proteins, are present in the mitochondrial matrix. Thus, the role of the mitochondrial Lon protease and the oxidized protein repair system methionine sulfoxide reductase is further addressed in the context of oxidative stress and aging.
Ugarte
Nicolas
N
Laboratoire de Biologie Cellulaire du Vieillissement, Université Pierre et Marie Paris, France.
Petropoulos
Isabelle
I
Friguet
Bertrand
B
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology
D024101:Mitochondrial Proteins