How do reactive oxygen species and calcium trigger mitochondrial membrane permeabilisation?

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.