1. How do reactive oxygen species and calcium trigger mitochondrial membrane permeabilisation?
- Author
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Tajeddine, Nicolas
- Subjects
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MITOCHONDRIAL membranes , *MEMBRANE permeability (Biology) , *ACTIVE oxygen in the body , *CELL death , *CANCER diagnosis , *CELL-mediated cytotoxicity - Abstract
Background Mitochondrial membrane permeabilisation (MMP) is classically considered as a point of no return in several forms of cell death and is involved in numerous diseases such as cancer, neurodegenerative disorders or ischemia/reperfusion injuries. Many studies established that reactive oxygen species (ROS) and Ca 2 + were the prominent inducers of MMP. However, the mechanisms connecting ROS and Ca 2 + to the players of MMP are still a matter of debate. Scope of review The aim of this review is to summarise the various studies related to the mechanisms of ROS- and Ca 2 + -induced MMP. Several lines of evidence suggest that ROS and Ca 2 + cooperate to induce MMP but the molecular details of the ROS–Ca 2 + -MMP network remain controversial. We then discuss recent data depicting this topic. Major conclusions Cytotoxic stimuli may be transduced within the cell by ROS and Ca 2 + increases. In most models, Ca 2 + and ROS can cooperate to induce MMP. Moreover, several data suggest that MMP increases mitochondrial Ca 2 + and ROS which therefore amplify the cytotoxic signal. Intriguingly, many reports have identified players of MMP as direct ROS targets. On the contrary, direct targets of Ca 2 + remain elusive. At the same time, the mechanisms by which mitochondrial Ca 2 + overload induces ROS generation are well documented. Upon these observations, we hypothesise that Ca 2 + cannot directly induce MMP and requires ROS production as a mandatory step. General significance Given the importance of Ca 2 + - and ROS-induced MMP in diseases, we expect that a better understanding of this process will lead to the development of novel therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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