Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging

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• 作者：Jenny K. Ngo ; Laura C.D. Pomatto ; Kelvin J.A. Davies
• 关键词：2D-PAGE ; two-dimensional polyacrylamide gel electrophoresis ; AAA ; ATPases associated with diverse cellular activities ; Aco1 ; Aconitase 1 ; Ccp1 ; mitochondrial cytochrome-c peroxidase ; CDDO ; 2-cyano-3 ; 12-dioxoolean-1 ; 9-dien-28-oic acid ; CDDO-Me ; methyl-2-cyano-3 ; 12-dioxooleana-1 ; 9(11)-dien-28-oate ; Clp ; caseinolytic protease ; ClpP ; core catalytic protease unit ; COX ; cytochrome c oxidase ; COX4-1 ; cytochrome c oxidase subunit IV isoform 1 ; COX4-2 ; cytochrome c oxidase subunit IV isoform 2 ; ERAD ; end
• 刊名：Redox Biology
• 出版年：2013
• 年：2013
• 卷：1
• 期：1
• 页码：258-264
• 全文大小：232 K

文摘

The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by 鈥榚lectron leakage鈥?from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation) or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.