Figure 2.

Under stress conditions, endoplasmic reticulum (ER) can act as a sensor and respond immediately. Meanwhile, if the stress intensity exceeds the adaptability of the ER, it will transmit death signals to mitochondria to initiate death events. The transduction can go through some pathways as follows: 1.ER perfuse Ca²⁺ into mitochondria and massive Ca²⁺ in mitochondria works as a death signal initiating cell death; 2. translocation of PACS1 from ER to mitochondria, which is along with the activation and translocation bid; 3. ceramide synthesis and accumulation causing the mitochondrial outer membrane permeabilization (MOMP), which results in the release of cytochrome c or other pro-apoptotic substances in inter membranes space. Also, as a molecule downstream of mitochondrial apoptosis, Fis1 can transmit apoptosis signal back to ER by cleaving BAP31. The ER-mitochondria-ER amplification loop of apoptotic signals can help to coordinate the death events between the two organelles.