Fig. 3: Mitochondrial fission is initiated by an increase in cytosolic calcium, which phosphorylates serine sites s600 and s616 and dephosphorylates serine sites s565 and s637 on Drp1 leading to its accumulation on the outer mitochondrial membrane (OMM).

Once translocated to the OMM, Drp1 can interact with several OMM receptors that are known to initiate mitophagy such as mitochondrial fission factor (Mff), mitochondrial fission protein 1 (Fis1) and mitochondrial dynamic proteins (MiD49/MiD51). Externalized cardiolipin (CL) has recently been shown to interact with and stabilize translocated Drp1.