Figure 8
MIEF and Mff coordinately work in Drp1-mediated mitochondrial fission. (i) A working model illustrating how Drp1-mediated mitochondrial fission is regulated by a sequential and coordinated interaction of MIEF and Mff with Drp1. (1) At the initial step of fission, Drp1 is recruited by MIEF (1a) and also by Mff (1b) from the cytosol to the mitochondrial surface. (2) At the mitochondrial surface, MIEF serves as an adaptor linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex. (3) MIEF promotes a direct binding of Drp1 to Mff possibly via reassembly of Drp1 from the trimeric complex to a functional dimeric Drp1-Mff complex. (4) Drp1-mediated fission is activated, resulting in mitochondrial division. MOM: mitochondrial outer membrane. (ii–iv) The model depicts the outcome of different cellular levels of MIEF: (ii) High MIEF levels inhibit fission, leading to a fusion phenotype by sequestering Drp1 in a dimeric Drp1-MIEF or trimeric Drp1-MIEF-Mff complex. (iii) Low/intermediate MIEF levels promote fission by facilitating a direct binding of Drp1 to Mff. (iv) In the absence of MIEFs, Drp1 is not effectively recruited to the MOM via MIEFs with the result that Mff itself cannot capture sufficient amount of Drp1. As a consequence, the balance of mitochondrial dynamics is shifted towards fusion, resulting in a moderate mitochondrial elongation phenotype.
