1. Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging☆
- Author
-
Kelvin J.A. Davies, Laura C.D. Pomatto, and Jenny K. Ngo
- Subjects
Fe/S, iron/SULFUR ,ERAD, endoplasmic reticulum-associated degradation ,Aging ,WI-38, human lung fibroblast ,Protease La ,Clinical Biochemistry ,Respiratory chain ,Adaptation, Biological ,Cellular homeostasis ,2D-PAGE, two-dimensional polyacrylamide gel electrophoresis ,AAA, ATPases associated with diverse cellular activities ,Review Article ,Mitochondrion ,medicine.disease_cause ,MPPβ, mitochondrial processing peptidase beta subunit ,Biochemistry ,HIF-1, hypoxia inducible factor-1 ,CDDO-Me, methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate ,Prx1, mitochondrial peroxiredoxin 1 ,SLLVY-AMC, N-succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin ,Chronic stress ,Disease ,lcsh:QH301-705.5 ,SOD2, mitochondrial superoxide dismutase 2 ,lcsh:R5-920 ,HsIVU, bacterial ATP-dependent protease ,Aco1, Aconitase 1 ,Mitochondria ,Up-Regulation ,COX, cytochrome c oxidase ,COX4-1, cytochrome c oxidase subunit IV isoform 1 ,HSP60 ,HSP60, heat shock protein 60 ,lcsh:Medicine (General) ,PRSS15, LON gene ,Senescence ,Pim1, ATP-dependent Lon protease from yeast ,SOD2 ,Biology ,SOD, cytosolic superoxide dismutase ,Ccp1, mitochondrial cytochrome-c peroxidase ,FRDA, Friedreich's ataxia ,Hormesis ,NRF-2, nuclear factor (erythroid-derived 2)-like 2 ,MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes ,medicine ,Clp, caseinolytic protease ,Animals ,Humans ,SPG13, hereditary spastic paraplegia ,Protease La, ATP-dependent protease ,Yjl200c, mitochondrial aconitase isozyme ,Adaptation ,COX4-2, cytochrome c oxidase subunit IV isoform 2 ,Organic Chemistry ,Lon Protease ,Nfκb, nuclear factor kappa-light-chain-enhancer of activated B csells ,HAART, highly active antiretroviral therapy ,CDDO, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid ,Oxidative Stress ,lcsh:Biology (General) ,bacteria ,HSP104, heat shock protein 104 ,ClpP, core catalytic protease unit ,Oxidative stress ,Protein degradation and oxidation - Abstract
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 ‘electron leakage’ 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.
- Published
- 2013