Two faces of TEMPO (2,2,6,6-tetramethylpiperidinyl-1-oxyl) - An antioxidant or a toxin?

2,2,6,6-Tetramethylpiperidine-1-oxyl, commonly known as TEMPO, is one of the compounds called nitroxides that are used in the chemical industry for synthesis of many organic compounds as well as for electrodes in allorganic radical batteries. Additionally, TEMPO is a widely used antioxidant in scientific studies. Technological progress and simultaneous care for the environment leads to resorting to new industrial methods which require the use of compounds that have not been fully tested for their impact on living organisms. Therefore, TEMPO may be an environmental pollutant and its effect on living organisms is not fully understood. The aim of our study was to determine the influence of TEMPO on the physiology, chronological lifespan and wide transcription changes of a eukaryotic model organism, namely the Saccharomyces cerevisiae yeast. For this purpose, we used the BY4741 wild-type and isogenic mutants with a disorder in the response to oxidative stress (sod1 Delta, sod2 Delta, yap1 Delta) and repair of DNA damage (rad52 Delta). We showed that supplementation with TEMPO inhibited the cell growth rate of all analyzed strains while simultaneously slowing down the aging of post-mitotic cells in the yeast population. In addition, TEMPO-treated yeast cells manifested a significantly increased level of metabolism in the wild-type and sod2 Delta strains. TEMPO also displayed genoprotective effect by reducing the number of DNA doublestrand breaks in cells. Here, we are the first to show the widespread effect of TEMPO on yeast. In conclusion, we have shown that, contrary to the commonly accepted notion, TEMPO has also a toxic effect, especially on active mitotic cells. We hypothesize that translation impairment or ribosome biogenesis disorder is likely to be considered secondary effects of TEMPO toxicity related to cell cycle arrest. Therefore, despite the growing interest in the use of this compound in the chemical industry, its toxic effect on the environment, especially biosphere, should be taken into account.