authors |
Busschaert, N; Park, SH; Baek, KH; Choi, YP; Park, J; Howe, ENW; Hiscock, JR; Karagiannidis, LE; Marques, I; Felix, V; Namkung, W; Sessler, JL; Gale, PA; Shin, I |
nationality |
International |
journal |
NATURE CHEMISTRY |
keywords |
TRANSMEMBRANE ANION TRANSPORTERS; SMALL-MOLECULE; CYTOCHROME-C; DEATH; ATPASE; ACIDIFICATION; TRAFFICKING; DISSECTION; LYSOSOMES; MEMBRANES |
abstract |
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 |
NATURE PUBLISHING GROUP |
issn |
1755-4330 |
year published |
2017 |
volume |
9 |
issue |
7 |
beginning page |
667 |
ending page |
675 |
digital object identifier (doi) |
10.1038/NCHEM.2706 |
web of science category |
Chemistry, Multidisciplinary |
subject category |
Chemistry |
unique article identifier |
WOS:000404056800014
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ciceco authors
impact metrics
journal analysis (jcr 2019):
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journal impact factor |
21.687 |
5 year journal impact factor |
24.633 |
category normalized journal impact factor percentile |
96.893 |
dimensions (citation analysis):
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altmetrics (social interaction):
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