Arsenite impinges on endoplasmic reticulum-mitochondria crosstalk to elicit mitochondrial ROS formation and downstream toxicity
| Autor: | Ester Zito, Andrea Guidarelli, Mara Fiorani, Orazio Cantoni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Cancer Research Arsenites Mitochondrion Endoplasmic Reticulum 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 5-triphosphate receptor Animals Humans Carcinogen Arsenite Ryanodine receptor Superoxide Endoplasmic reticulum Cell biology Mitochondria Crosstalk (biology) 030104 developmental biology chemistry Inositol-1 4 5-triphosphate receptor Mitochondrial Ca(2+) Mitochondrial superoxide 030220 oncology & carcinogenesis Inositol-1 Reactive Oxygen Species |
| Popis: | Arsenite is an important carcinogen and toxic compound, causing various deleterious effects through multiple mechanisms. In this review, we focused on mitochondrial ROS (mitoROS) and discussed on the mechanisms mediating their formation. The metalloid promotes direct effects in mitochondria, resulting in superoxide formation only under conditions of increased mitochondrial Ca2+ concentration ([Ca2+]m). In this perspective, the time of exposure and concentration requirements for arsenite were largely conditioned by other effects of the metalloid in specific sites of the endoplasmic reticulum (ER). Arsenite induced a slow and limited mobilization of Ca2+ from IP3R via a saturable mechanism, failing to increase the [Ca2+]m. This effect was however associated with the triggering of an intraluminal crosstalk between the IP3R and the ryanodine receptor (RyR), causing a large and concentration dependent release of Ca2+ from RyR and a parallel increase in [Ca2+]m. Thus, the Ca2+-dependent mitoO2-. formation appears to be conditioned by the spatial/functional organization of the ER/mitochondria network and RyR expression. We also speculate on the possibility that the ER stress response might regulate the above effects on the intraluminal crosstalk between the IP3R and the RyR via oxidation of critical thiols mediated by the H2O2 locally released by oxidoreductin 1α. |
| Databáze: | OpenAIRE |
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