Membrane Dynamics: MIEF1 Mingles with Mitochondria

RESEARCH HIGHLIGHTS

MEMBRANE DYNAMICS MIEF1 mingles with mitochondria The morphology of mitochondria, fusion, resulting in an elongated DRP1 recruitment did not require which is determined by a dynamic morphology. This was also seen FIS1, MFN2 or mitochondrial fission MIEF1 … has cycle of membrane fusion and fis- when MIEF1 was overexpressed in an factor (MFF), another recently iden- a dual role sion events, is crucial for normal in vivo cell fusion assay. Conversely, tified protein that promotes DRP1 in inhibiting functioning of this organelle. Zhao RNA interference-mediated depletion mitochondrial localization. et al. have now identified a new com- of MIEF1 increased mitochondrial The fact that MIEF1 recruits fission and ponent of the human mitochondrial fragmentation. These effects on DRP1 to mitochondria might promoting outer membrane, mitochondrial mitochondrial morphology were suggest that it would promote fusion. elongation factor 1 (MIEF1), which independent of mitofusin 2 (MFN2), DRP1‑mediated fission of mitochon- has a dual role in inhibiting fission a well-characterized regulator of the dria. However, Zhao et al. find that and promoting fusion. fusion pathway. MIEF1 impairs DRP1 binding to After identifying MIEF1 as an Mitochondrial fission requires the GTP, which would be predicted integral protein at the mitochondrial GTPase dynamin-related protein 1 to inhibit DRP1’s effects on fission. outer membrane, Zhao et al. observed (DRP1; also known as DNM1L), Co-immunoprecipitation analysis that overexpression of MIEF1 in which predominantly localizes to showed that MIEF1 also associates 293T cells increased mitochondrial the cytoplasm and must be actively with FIS1, independently of DRP1 recruited to the mitochondrial binding, and increased levels of membrane. In yeast, mitochondrial FIS1 partially reverted the effects of fission 1 (Fis1) is thought to act as MIEF1 overexpression on fusion. its mitochondrial receptor. However, Thus, MIEF1 may promote mito- this does not hold true in vertebrates, chondrial fusion through a mecha- and efforts to work out how verte- nism that is independent of MFN2 brate DRP1 reaches mitochondria but that is kept in check by FIS1. have identified few regulators so MIEF1 seems to provide a means far. Therefore, the authors sought to of regulating mitochondrial dynamics determine whether MIEF1 might that is unique to vertebrates. It will be be the vertebrate receptor for DRP1. intriguing to learn more about how They found that MIEF1 and endog- it exerts its dual effects on fission and enous DRP1 colocalized on mito- fusion, and how its efforts in recruit- chondria and they also associated by ing DRP1 are coordinated with other co-immunoprecipitation. Moreover, factors, such as MFF. overexpression of MIEF1 resulted Alison Schuldt in increased association of DRP1

with mitochondria. The authors ORIGINAL RESEARCH PAPER Zhao, J. et al. An in vivo cell fusion assay in which mitochondria are mapped the region of MIEF1 that is Human MIEF1 recruits Drp1 to mitochondrial labelled in red or green, with mitochondrial fusion important for this association and outer membranes and promotes mitochondrial indicated in yellow. Polykaryon cells (nuclei labelled in fusion rather than fission. EMBO J. blue) expressing tagged MIEF1 (a) showed increased showed that overexpressed MIEF1 24 Jun 2011 (doi:10.1038/emboj.2011.198) mitochondrial fusion compared with control cells affects mitochondrial morphology FURTHER READING Westermann, B. expressing an empty vector (b). Image is reproduced, only if it retains this DRP1‑binding Mitochondrial fusion and fission in cell life and with permission, from Zhao, J. et al. © (2011) Macmillan death. Nature Rev. Mol. Cell Biol. 11, 872–884 (2010) Publishers Ltd. All rights reserved. region. The effects of MIEF1 on