Nature Chemistry
Nature Chemistry
5 years ago

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations
Jinhong Park, Wan Namkung, Jonathan L. Sessler, Louise E. Karagiannidis, Nathalie Busschaert, Igor Marques, Vítor Félix, Seong-Hyun Park, Yoon Pyo Choi, Injae Shin, Philip A. Gale, Kyung-Hwa Baek, Jennifer R. Hiscock, Ethan N. W. Howe
Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Publisher URL: http://dx.doi.org/10.1038/nchem.2706

DOI: 10.1038/nchem.2706

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.