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Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division
Authors:Bego?a Ugarte-Uribe  Hans-Michael Müller  Miki Otsuki  Walter Nickel  Ana J. García-Sáez
Affiliation:From the Max-Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany.;the §Interfaculty Institute of Biochemistry, University of Tübingen, 72076 Tübingen, Germany, and ;the Heidelberg University Biochemistry Center, 69120 Heidelberg, Germany
Abstract: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.
Keywords:GTPase   Liposome   Membrane Biophysics   Membrane Reconstitution   Mitochondria   Giant Unilamellar Vesicles   Membrane Curvature   Membrane Fission
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