Protein damage and death by radiation in Escherichia coli and Deinococcus radiodurans

Abstract

Deinococcus radiodurans is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in D. radiodurans as well as in standard and evolved resistant strains of Escherichia coli exposed to ionizing radiation or UVC light and found a consistent correlation with cell killing. The unique quantitative relationship between incurred PC and cell death holds over the entire range of killing for all tested bacteria and for both lethal agents, meaning that both bacterial species are equally sensitive to PC. We show that the extraordinary robustness of D. radiodurans depends on efficient proteome protection (but not DNA protection) against constitutive and radiationinduced PC consisting of low molecular weight cytosolic compounds. Remarkably, experimental evolution of resistance to ionizing radiation in E. coli coevolves with protection against PC. The decline in biosynthetic efficacy of the cellular proteome, as measured by the loss of reproduction of undamaged bacteriophage λ in irradiated standard and evolved ionizing radiation-resistant E. coli, correlates with radiation-induced oxidative damage to host cells and their sensitivity to ionizing radiation. This correlation suggests that cell death by radiation is caused primarily by oxidative damage with consequential loss of maintenance activities including DNA repair.carbonylation | robustness | UV

Extreme anti-oxidant protection against ionizing radiation in bdelloid rotifers

“…Although the biochemical identity of the bdelloid anti-oxidant system remains to be established and may or may not be like that of D. radiodurans (11,12), some of its features may be specified on the basis of present knowledge: (i) As irradiation was done on ice, the system is present constitutively, consistent with the lack of a dose-rate effect for fecundity reduction (Fig. 1A).…”

Iron enzyme ribulose-5-phosphate 3-epimerase in Escherichia coli is rapidly damaged by hydrogen peroxide but can be protected by manganese

“…Catalase and peroxidase activities are sufficient to cope with the H 2 O 2 that is formed as a by-product of aerobic metabolism, but the diffusion of H 2 O 2 into the cell from environmental sources can drive its steadystate levels above the threshold of toxicity (29). Recent studies from several laboratories indicate that protein damage is likely to determine the fate of oxidant-exposed cells (30)(31)(32)(33). Rpe, and probably mononuclear Fe enzymes in general, now join Fe-S dehydratases as primary classes of enzymes that H 2 O 2 damages.…”

Vieillissement : la chimie d’une horloge biologique flexible

“…Mais une thérapie préventive serait bien préférable à cette thérapie réparatrice apportant de nouvelles protéines, car elle assurerait la pérennité du processus naturel de renouvellement du protéome en renforçant les voies de renouvellement des protéines (dégradation sélective par le protéasome, autophagosome, chaperons, et synthèse de novo). C'est exactement la stratégie choisie par l'évolution de la résilience des organismes robustes [8,9].…”

“…Nous avons récemment établi que chez les bactéries [8] et chez les animaux [9], la morbidité et la mortalité cellulaires corrèlent avec l'accumulation des protéines endommagées par oxydation. D'autre part, la mort cellulaire par irradiation est fonction non pas tant des dommages subis par l'ADN -support de l'information -que de ceux subis par les protéines effectrices [8,11].…”

“…D'autre part, la mort cellulaire par irradiation est fonction non pas tant des dommages subis par l'ADN -support de l'information -que de ceux subis par les protéines effectrices [8,11]. Ce n'est pas surprenant : ce sont des protéines qui réparent l'ADN, et pas l'inverse.…”