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Access through your institution Buy or subscribe _Nat. Chem._ 10.1038/nchem.2021 The maintenance of ion homeostasis is crucial to ensure cell viability. Disrupting this balance through

increased ion flux into cells triggers programed cell death, a process known as apoptosis. Prodigiosin is a natural product that promotes cancer cell death by allowing the influx of HCl into

cells across what are normally impermeable membranes. Many groups have synthesized similar ion transporters, but few have been successful in mimicking the biological effects of prodigiosin.

Ko _et al_. synthesized pyridine diamide–strapped calixpyrroles, which transport chloride and sodium ions across lipophilic membranes. Using ion-specific fluorescent probes, the authors

observed an increase in the intracellular levels of chloride and sodium in mammalian cells when the small-molecule transporter was present. These cell lines exhibited reduced cellular

viability features consistent with caspase-mediated apoptosis, including increased reactive oxygen species, mitochondrial cytochrome _c_ release and activation of caspases. The authors

verified the requirement of sodium and chloride for promoting apoptosis. For instance, they showed that the frequency of cell death decreased when the transporter was added to cells cultured

in a chloride- or sodium-free medium. Finally, the authors found that sodium chloride influx and ROS production occurred earlier than the first indication of cell death, confirming that the

influx of ions into cells promotes apoptosis. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal

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Authors * Grant Miura View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Miura, G. Death by ions. _Nat Chem Biol_ 10, 795 (2014). https://doi.org/10.1038/nchembio.1648 Download citation * Published: 17 September 2014 * Issue Date: October 2014 * DOI:

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