However, the question remains of how mitochondrial ROS trigger platelet apoptosis? It has been previously reported that mitochondria-derived ROS plays a pivotal role in triggering apoptosis in various cell types [14,23,24]. It has been reported that mitochondria-derived superoxide anions play a pro-apoptotic role by causing the down-regulation and degradation of the Bcl-2 protein in an ubiquitin proteasomal-dependent pathway [50].