Mitofissin promotes mitochondrial fission. (A) During mitophagy, SARs such as Atg32 or Atg43 designate a region of mitochondria for degradation, and orchestrate phagophore formation and expansion at this location. Mitofissin in the IMS participates in membrane remodeling to induce mitochondrial fission, separating the targeted region of mitochondria from the rest of organelle body and generating small mitochondrial fragments that can be sequestered into autophagosomes. (B) In the absence of mitofissin, the SARs-marked region remains connected to the main body of mitochondria, resulting in the formation of mitochondrial protrusions toward the PAS. (C) Membrane fission by mitofissin in vitro. Lipid nanotubes (left) and supported lipid bilayers (right) are severed and fragmented, respectively, by the action of mitofissin, which undergoes disassembly from an octamer to smaller oligomeric form. HS-AFM stands for high-speed atomic force microscopy.