Editorial: Ion and Water Transport in Cell Death.
Ontology highlight
ABSTRACT:
SUBMITTER: Ritter M
PROVIDER: S-EPMC8458750 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Editorial: Ion and Water Transport in Cell Death.
Ritter Markus M Mongin Alexander A AA Valenti Giovanna G Okada Yasunobu Y
Frontiers in cell and developmental biology 20210909
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Project description:Recently, we showed that synthetic anion transporters DSC4P-1 and SA-3 had activity related to cancer cell death. They were found to increase intracellular chloride and sodium ion concentrations. They were also found to induce apoptosis (DSC4P-1) and both induce apoptosis and inhibit autophagy (SA-3). However, determinants underlying these phenomenological findings were not elucidated. The absence of mechanistic understanding has limited the development of yet-improved systems. Here, we show that three synthetic anion transporters, DSC4P-1, SA-3, and 8FC4P, induce osmotic stress in cells by increasing intracellular ion concentrations. This triggers the generation of reactive oxygen species via a sequential process and promotes caspase-dependent apoptosis. In addition, two of the transporters, SA-3 and 8FC4P, induce autophagy by increasing the cytosolic calcium ion concentration promoted by osmotic stress. However, they eventually inhibit the autophagy process as a result of their ability to disrupt lysosome function through a transporter-mediated decrease in a lysosomal chloride ion concentration and an increase in the lysosomal pH.
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