Models for mitochondrial fission in vertebrates. Classical model, Fis1 acts as the mitochondrial receptor for Drp1 promoting fission. Extended model, Fis1, Mff and/or MIEF1/MiD51/Mid49 recruit Drp1 to the mitochondria. The Mff–Drp1 complex promotes mitochondrial fission. In contrast, the MIEF1/Mid49/51–Drp1 sequesters Drp1, inhibits Drp1 function and promotes fusion in an Mfn2-independent manner. Mitochondria become elongated. In an apparently mutually exclusive manner, MIEF1/MiD51 can also form a complex with Fis1 (MiD49 was omitted here as a MiD49–Fis1 complex was not demonstrated to exist yet). By that, the inhibitory effect of MIEF1/MiD51 on Drp1 function is reduced and hence mitochondrial fission is indirectly promoted by Fis1. Active Drp1, green. Inhibited Drp1, red.