A dimeric equilibrium intermediate nucleates Drp1 reassembly on mitochondrial membranes for fission

• DOI: 10.1091/mbc.e14-02-0728
• Publication Date: 2014-05-01T02:41:39Z
• Authors: Patrick J. Macdonald; Natalia Stepanyants; Niharika Mehrotra; Jason A. Mears; Xin Qi; Hiromi Sesaki; Rajesh Ramachandran
• Keywords: DNM1L

The GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial division, but the mechanisms remain poorly understood. Much of what is attributed to Drp1’s mechanism action in membrane fission parallels that prototypical dynamin endocytic vesicle scission. Unlike case for dynamin, however, no lipid target Drp1 activation at mitochondria has been identified. In addition, oligomerization properties have not well established. We show mitochondria-specific cardiolipin a potent stimulator activity, as tubulation. establish further under physiological conditions, coexists two morphologically distinct polymeric species, one nucleotide bound solution and other associated, which equilibrate via dimeric assembly intermediate. With mutations, C300A C505A, shift polymerization equilibria opposite directions, we demonstrate dimers, multimers, potentiate reassembly reorganization remodeling both vitro vivo.