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While monensin is used widely in animals, toxicity impedes its use in humans. Nonetheless, given its potency, understanding its mode of action would reveal vulnerable aspects of the parasite that can be exploited for drug development. We previously established that monensin induces<jats:italic>Toxoplasma<\/jats:italic>to undergo cell cycle arrest and an autophagy-like cell death. Interestingly, these effects are dependent on the mitochondrion-localized TgMSH-1 protein, suggesting that monensin disrupts mitochondrial function. We demonstrate that monensin treatment results in decreased mitochondrial membrane potential and altered morphology. These effects are mitigated by the antioxidant compound N-acetyl-cysteine suggesting that monensin causes an oxidative stress, which was indeed the case based on direct detection of reactive oxygen species. Moreover, over-expression of the antioxidant proteins glutaredoxin and peroxiredoxin 2 protect<jats:italic>Toxoplasma<\/jats:italic>from the deleterious effects of monensin. Thus, our studies show that the effects of monensin on<jats:italic>Toxoplasma<\/jats:italic>are due to a disruption of mitochondrial function caused by the induction of an oxidative stress and implicate parasite redox biology as a viable target for the development of drugs against<jats:italic>Toxoplasma<\/jats:italic>and related pathogenic parasites.<\/jats:p>","DOI":"10.1038\/srep22997","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T10:05:50Z","timestamp":1458036350000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function"],"prefix":"10.1038","volume":"6","author":[{"given":"Robert A.","family":"Charvat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Arrizabalaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"BFsrep22997_CR1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0140-6736(96)11105-3","volume":"350","author":"WR Bowie","year":"1997","unstructured":"Bowie, W. 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