Mitochondrial fusion and fission. (A) Mitochondrial fusion occurs in two distinct steps, both mediated by large GTP-hydrolyzing enzymes of the dynamin superfamily. MFN1 and MFN2 mediate fusion of the mitochondrial outer membrane (OMM). Then, OPA1 mediates fusion of the inner membrane (IMM), which results in mixing of matrix components. Although OPA1 is present on opposing IMMs, it is not required to be present on both membranes. (B) Mitochondrial fission is a multistep process. In the initial phase, actin and the ER associate with the mitochondrial tubule. The ER wraps around and constricts the mitochondrion. Receptors on the mitochondrial outer membrane (not shown) recruit cytosolic DRP1 to this constriction site. Multiple DRP1 molecules oligomerize around the mitochondrion to form a ring-shaped structure that further constricts and severs the mitochondrial tubule.