Functional organization of the endoplasmic reticulum dictates the susceptibility of target cells to arsenite-induced mitochondrial superoxide formation, mitochondrial dysfunction and apoptosis
| Autor: | Ester Zito, Andrea Guidarelli, Ersilia Varone, Andrea Spina, Alessia Catalani, Mara Fiorani, Stefano Fumagalli, Orazio Cantoni |
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| Rok vydání: | 2021 |
| Předmět: |
Arsenites
Cell Survival Apoptosis Mitochondrion Toxicology Endoplasmic Reticulum chemistry.chemical_compound Superoxides 5-triphosphate receptor Cell Line Tumor medicine Humans Receptor Arsenite chemistry.chemical_classification Reactive oxygen species Ryanodine receptor Endoplasmic reticulum 4 5-triphosphate receptor Inositol-1 Mitochondrial Ca(2+) Mitochondrial superoxide Ryanodine Receptor Calcium Release Channel General Medicine medicine.disease Cell biology Mitochondria Mitochondrial toxicity chemistry Gene Expression Regulation Calcium Food Science |
| Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 156 |
| ISSN: | 1873-6351 |
| Popis: | Arsenite induces many critical effects associated with the formation of reactive oxygen species (ROS) through different mechanisms. We focused on the Ca2+-dependent mitochondrial superoxide (mitoO2-.) formation and addressed questions on the effects of low concentrations of arsenite on the mobilization of the cation from the endoplasmic reticulum and the resulting mitochondrial accumulation. Using various differentiated and undifferentiated cell types uniquely expressing the inositol-1, 4, 5-triphosphate receptor (IP3R), or both the IP3R and the ryanodine receptor (RyR), we determined that expression of this second Ca2+ channel is an absolute requirement for mitoO2-. formation and for the ensuing mitochondrial dysfunction and downstream apoptosis. In arsenite-treated cells, RyR was recruited after IP3R stimulation and agonist studies indicated that in these cells RyR is in close apposition with mitochondria. It was also interesting to observe that arsenite fails to promote mitochondrial Ca2+ accumulation, mitoO2-. formation, mitochondrial toxicity in RyR-devoid cells, in which the IP3R is in close contact with the mitochondria. We therefore conclude that low dose arsenite-induced mitoO2- formation and the resulting mitochondrial dysfunction and toxicity, are prerequisite of cell types expressing the RyR in close apposition with mitochondria. |
| Databáze: | OpenAIRE |
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