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The therapeutic potential of mitochondrial toxins

Abstract

When screening active compounds by phenotypic assays, we often encounter mitochondrial toxins, which are compounds that can affect mitochondrial functions. In normal cells, these toxins may have relatively low toxicity but can nonetheless show measurable effects even at low concentrations. On the other hand, in animals, mitochondrial toxins can exert severe toxicity. Mitochondrial toxins that act as inhibitors of respiratory chain complexes in oxidative phosphorylation (OXPHOS) are typically avoided during drug discovery efforts, as such compounds can directly promote lethal inhibition of pulmonary respiration. However, mitochondrial toxins could in fact have beneficial therapeutic effects. Anti-cancer strategies that target mitochondrial functions, particularly OXPHOS, have received increasing attention in recent years. In this review article we examine the significance of OXPHOS inhibitors as anti-cancer drug candidates and discuss compounds having microbial origins.

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Acknowledgements

We thank Dr. Takumi Watanabe, Dr. Hikaru Abe, and all collaborators for the intervenolin project. This work was supported in part by the Project for Cancer Research and Therapeutic Evolution (P-CREATE) of the Japan Agency for Medical Research and Development, AMED: 20cm010623h0005 to M.K.

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Correspondence to Manabu Kawada.

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Kawada, M., Amemiya, M., Yoshida, J. et al. The therapeutic potential of mitochondrial toxins. J Antibiot 74, 696–705 (2021). https://doi.org/10.1038/s41429-021-00436-z

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