Abstract
GTPase dynamin-related protein (Dnm1)-mediated membrane fission is an important membrane remodeling event supporting the proliferation and housekeeping function of semiautonomous organelles such as the mitochondrion and peroxisome. Dnm1 is at the heart of the membrane fission machinery, which constricts the neck of the dividing organelles. Similar to classical dynamin protein, Dnm1 hydrolyzes GTP, an energy source, thereby generating a constriction force to sever the neck. To complete this process, replenishment of GTP to Dnm1 needs to be done in a regulated and timely manner. However, the molecular mechanisms that provide GTP to Dnm1 are not known. In this review, we present the evidence for emerging consensus on Dnm1 function and our recent work demonstrating that: (1) The ATP-GTP converting, nucleoside diphosphate kinase-like protein DYNAMO1 is present in the mitochondrial and peroxisomal membrane fission machinery. (2) DYNAMO1 facilitates enzyme kinetics of Dnm1 and locally provides GTP to Dnm1 on the membrane fission machinery. (3) The membrane fission machinery spends more GTP on constriction than on recruitment, as seen by the in vivo experiments and in vitro reconstitution of the Dnm1 structure. Summarizing these data, this review would help to understand the mechanism by which Dnm1 promotes membrane fission using GTP as an energy source. We also discuss how future research might solve the remaining open questions regarding the energy issues presently under discussion.
