FIGURE 9.

A proposed model for mitochondrial recruitment of Drp1 through MIEFs (MIEF1 and MIEF2) and Mff. Drp1 exists in the cytosol as a reservoir of tetramers and higher order oligomers in active and inactive states. MIEFs can recruit all assembly forms including active and inactive forms of Drp1 to mitochondria. Under physiological conditions, MIEFs bind to active forms of Drp1 facilitating fission (A); MIEFs serve as a platform to facilitate the interaction between Mff and Drp1 (B); However, high levels of MIEFs give rise to Drp1 aggregates and sequester the protein in an inactive state resulting in the inhibition of fission (C). In contrast, Mff alone preferentially recruits GTPase-active and fission-competent forms of Drp1 to mitochondria promoting fission.