Is Overoxidation of Peroxiredoxin Physiologically Significant?

Abstract

Eukaryotic peroxiredoxins are highly susceptible to sulfinic acid formation. This overoxidation, which is thought to convert peroxiredoxins into chaperones, can be reversed by sulfiredoxins. Several organisms, including Caenorhabditis elegans, lack sulfiredoxins but encode sestrins, proteins proposed to be functionally equivalent. We induced peroxiredoxin overoxidation in C. elegans with a short peroxide pulse. We found that reduction of overoxidized peroxiredoxin 2 (PRDX-2) was extremely slow and sestrin-independent, strongly implying that worms lack an efficient repair system. Analysis of PRDX-2's overoxidation status during C. elegans lifespan revealed no accumulation of overoxidized PRDX-2 at any point, questioning whether PRDX-2 overoxidation in worms is physiologically relevant. Antioxid. Redox Signal. 14, 725-730.

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

“…We were able to demonstrate that the C. elegans peroxiredoxin PRDX-2, previously shown to be involved in peroxide and heavy metal resistance (45), is of major importance to this function. Peroxiredoxins are a class of antioxidant proteins characterized by their high susceptibility to cysteine oxidation (46,47). PRDX-2 is a typical 2-Cys peroxiredoxin (45), of which the active, oxidized form exists as a homodimer (48).…”

Peroxiredoxins in Parasites

“…Also, although C. elegans possesses a sestrin homolog and a Prx sensitive to overoxidation, its subsequent reduction is very slow. Furthermore, under ordinary conditions, accumulation of the overoxidized Prx could be detected neither in wild-type C. elegans nor in a sestrin deletion strain (248).…”

Role of Reactive Oxygen Species-Mediated Signaling in Aging

“…Consistent with this possibility, a neuronal Prx was identified in D. melanogaster as a downstream target of the insulin signalingregulated transcription factor FOXO, which is involved in the increased resistance to H 2 O 2 and the lifespan extension effect of CR (41). It should be noted, however, that some organisms (e.g., C. elegans), lack any Srx gene or Srx-like enzyme activity and do not show an increase in Prx hyperoxidation with age (70). Thus, the induction of Srx by CR observed in yeast is unlikely to mediate CR-induced increases in lifespan in these organisms.…”