Human MIEF1 recruits Drp1 to mitochondrial outer membranes and promotes mitochondrial fusion rather than fission
Open Access
- 24 June 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 30 (14), 2762-2778
- https://doi.org/10.1038/emboj.2011.198
Abstract
Mitochondrial morphology is controlled by two opposing processes: fusion and fission. Drp1 (dynamin‐related protein 1) and hFis1 are two key players of mitochondrial fission, but how Drp1 is recruited to mitochondria and how Drp1‐mediated mitochondrial fission is regulated in mammals is poorly understood. Here, we identify the vertebrate‐specific protein MIEF1 (mitochondrial elongation factor 1; independently identified as MiD51), which is anchored to the outer mitochondrial membrane. Elevated MIEF1 levels induce extensive mitochondrial fusion, whereas depletion of MIEF1 causes mitochondrial fragmentation. MIEF1 interacts with and recruits Drp1 to mitochondria in a manner independent of hFis1, Mff (mitochondrial fission factor) and Mfn2 (mitofusin 2), but inhibits Drp1 activity, thus executing a negative effect on mitochondrial fission. MIEF1 also interacts with hFis1 and elevated hFis1 levels partially reverse the MIEF1‐induced fusion phenotype. In addition to inhibiting Drp1, MIEF1 also actively promotes fusion, but in a manner distinct from mitofusins. In conclusion, our findings uncover a novel mechanism which controls the mitochondrial fusion–fission machinery in vertebrates. As MIEF1 is vertebrate‐specific, these data also reveal important differences between yeast and vertebrates in the regulation of mitochondrial dynamics.Keywords
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