Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. The study shows that Fis1 and Mff are essential for mitochondrial fission by recruiting the GTPase Drp1 to the mitochondrial outer membrane. Drp1 forms puncta on mitochondria, which constrict the mitochondrial tubule to mediate fission. While Fis1 was initially proposed as a receptor for Drp1, recent studies suggest that Mff is the stronger candidate. MiD49 and MiD51, which are also involved in mitochondrial fission, have conflicting evidence regarding their role. However, the study demonstrates that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. The results indicate that multiple receptors can recruit Drp1 to mediate mitochondrial fission. The study also shows that Fis1 and Mff can function independently to regulate mitochondrial fission in mouse embryonic fibroblasts (MEFs). Additionally, the study finds that MiD49 and MiD51 can mediate mitochondrial fission in the absence of Fis1 and Mff. The findings suggest that these proteins play a critical role in mitochondrial fission by recruiting Drp1 to the mitochondrial surface. The study also highlights the importance of Drp1 phosphorylation in mitochondrial fission, with MiD49 and MiD51 preferentially binding to the S637-PO4 form of Drp1. Overall, the study provides new insights into the mechanisms of mitochondrial fission and the roles of Fis1, Mff, MiD49, and MiD51 in this process.Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. The study shows that Fis1 and Mff are essential for mitochondrial fission by recruiting the GTPase Drp1 to the mitochondrial outer membrane. Drp1 forms puncta on mitochondria, which constrict the mitochondrial tubule to mediate fission. While Fis1 was initially proposed as a receptor for Drp1, recent studies suggest that Mff is the stronger candidate. MiD49 and MiD51, which are also involved in mitochondrial fission, have conflicting evidence regarding their role. However, the study demonstrates that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. The results indicate that multiple receptors can recruit Drp1 to mediate mitochondrial fission. The study also shows that Fis1 and Mff can function independently to regulate mitochondrial fission in mouse embryonic fibroblasts (MEFs). Additionally, the study finds that MiD49 and MiD51 can mediate mitochondrial fission in the absence of Fis1 and Mff. The findings suggest that these proteins play a critical role in mitochondrial fission by recruiting Drp1 to the mitochondrial surface. The study also highlights the importance of Drp1 phosphorylation in mitochondrial fission, with MiD49 and MiD51 preferentially binding to the S637-PO4 form of Drp1. Overall, the study provides new insights into the mechanisms of mitochondrial fission and the roles of Fis1, Mff, MiD49, and MiD51 in this process.