Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function

Robert A. Charvat, Gustavo Arrizabalaga

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The ionophore monensin displays potent activities against several coccidian parasites of veterinary and medical importance including the opportunistic pathogen of humans, Toxoplasma gondii. 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 Toxoplasma 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 Toxoplasma from the deleterious effects of monensin. Thus, our studies show that the effects of monensin on Toxoplasma 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 Toxoplasma and related pathogenic parasites.

Original languageEnglish (US)
Article number22997
JournalScientific Reports
Volume6
DOIs
StatePublished - Mar 15 2016

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Monensin
Toxoplasma
Oxidative Stress
Parasites
Antioxidants
Glutaredoxins
Peroxiredoxins
Mitochondrial Membrane Potential
Ionophores
Autophagy
Cell Cycle Checkpoints
Pharmaceutical Preparations
Oxidation-Reduction
Cysteine
Reactive Oxygen Species
Mitochondria
Proteins
Cell Death

ASJC Scopus subject areas

  • General

Cite this

Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function. / Charvat, Robert A.; Arrizabalaga, Gustavo.

In: Scientific Reports, Vol. 6, 22997, 15.03.2016.

Research output: Contribution to journalArticle

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