Abstract
Dynamin-related protein 1 (Drp1) is essential for mitochondrial and peroxisomal fission. Recent studies propose that Drp1 does not sever but rather constricts mitochondrial membranes allowing dynamin 2 (Dnm2) to execute final scission. Here, we report that unlike Drp1, Dnm2 is dispensable for peroxisomal and mitochondrial fission, as these events occurred in Dnm2 knockout cells. Fission events were also observed in mouse embryonic fibroblasts lacking Dnm1, 2 and 3. Using reconstitution experiments on preformed membrane tubes, we show that Drp1 alone both constricts and severs membrane tubes. Scission required the membrane binding, self-assembling and GTPase activities of Drp1 and occurred on tubes up to 250 nm in radius. In contrast, Dnm2 exhibited severely restricted fission capacity with occasional severing of tubes below 50 nm in radius. We conclude that Drp1 has both membrane constricting and severing abilities and is the dominant dynamin performing mitochondrial and peroxisomal fission.
Highlights
Dynamin-related protein 1 (Drp1) is essential for mitochondrial and peroxisomal fission
Given the model proposing the cooperation between Drp[1] and Dnm[2] in mitochondrial division, we sought to address if the same was applicable for peroxisomes
Expression of Dnm[2] in Dnm2KO/Drp1KO cells was unable to rescue peroxisomal fission defects; only after the additional re-expression of Drp[1] were peroxisomes converted to their spherical shape (Fig. 1d)
Summary
Dynamin-related protein 1 (Drp1) is essential for mitochondrial and peroxisomal fission. Cellular cues that regulate their division are relatively less clear Both mitochondrial and peroxisomal fission is facilitated by dynaminrelated protein 1 (Drp1)[6,7,8,9,10], a member of the dynamin superfamily of proteins that self-assemble as helical scaffolds and utilizes the energy from GTP hydrolysis to constrict and remodel tubular membrane intermediates[11,12]. A recent study puts the classical dynamin 2 (Dnm2) at the center of mitochondrial fission since knockdown of Dnm[2] resulted in significant mitochondrial elongation, with Drp[1] accumulating at both ends of highly constricted tubular membrane intermediates[21] This pointed toward the possibility that Dnm[2] severs the final single-membrane tube between two Drp[1] scaffolds and was supported by Dnm[2] localization studies. Reconstitution experiments show that Drp[1] can bind, constrict, and sever preformed membrane tubules alone in vitro
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
