Figure 3.

Schematic depiction of mitochondrial fusion and fission in neurons. Mitochondrial fusion relies on membrane proteins Mfn1/2 and OPA1 residing in the OMM and the IMM, respectively. Mfn1 and Mfn2 form homo-oligomeric (Mfn1-Mfn1 or Mfn2-Mfn2) and hetero-oligomeric (Mfn1-Mfn2) complexes in trans between the opposing mitochondria to induce the OMM fusion. The long and short forms of OPA1 synergistically catalyze the tethering and fusion of the IMM. Mitochondrial fission begins with the ER contacts with the OMM at the ER-mitochondria contact sites, and ER wraps tightly around the mitochondria to form constrictions. The cytosolic Drp1 is subsequently recruited to the OMM via multiple membrane adaptors MiD51, MiD49, Fis1, and Mff. Drp1 oligomerizes at the ER-marked pre-constriction sites, forming a ring-like structure around the mitochondria for further membrane constriction.