Fig. 9.

Model for CL-dependent Drp1-catalyzed stress-induced mitochondrial fission. (Top) Proposed pathway for CL externalization-induced Drp1 self-assembly and mitochondrial hyperfragmentation toward mitophagy. (Middle and Bottom) Specific interactions of the VD MoRF-1 and MoRF-2 motifs with CL elicit a disorder-to-order transition that enables VD membrane insertion and stabilization of Drp1 self-assembly toward hemifission and fission. Certain MoRF-1 and MoRF-2 mutants are impaired in this transition, leading to weakened or entirely abrogated Drp1–membrane interactions. Unbound MOM CL is converted to PA by the action of mitochondrial phospholipase D. Profusogenic PA stimulates Mfn1/2 activity, leading to mitochondrial hyperfusion and, in the case of W552 mutants, the formation of mitophagy-resistant donut mitochondria.