Dynamin-related protein 1 (Drp1) promotes structural intermediates of membrane division*
Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reco...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 31, 2014
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| In: |
The journal of biological chemistry
Year: 2014, Volume: 289, Issue: 44, Pages: 30645-30656 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.575779 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M114.575779 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820372690 
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| Author Notes: | Begoña Ugarte-Uribe, Hans-Michael Müller, Miki Otsuki, Walter Nickel, and Ana J. García-Sáez |
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| 520 | |a Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reconstituted and directly visualized Drp1 activity in giant unilamellar vesicles. We quantified the effect of lipid composition and GTP on membrane binding and remodeling activity by fluorescence confocal microscopy and flow cytometry. In contrast to other dynamin relatives, Drp1 bound to both curved and flat membranes even in the absence of nucleotides. We also found that Drp1 induced membrane tubulation that was stimulated by cardiolipin. Moreover, Drp1 promoted membrane tethering dependent on the intrinsic curvature of the membrane lipids and on GTP. Interestingly, Drp1 concentrated at membrane contact surfaces and, in the presence of GTP, formed discrete clusters on the vesicles. Our findings support a role of Drp1 not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission. | ||
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