Bui et al. investigate how a dynamin-related GTPase is recruited to the mitochondrial outer membrane to drive mitochondrial fission.
Dynamin binds directly to the plasma membrane to remodel the lipid bilayer during endocytosis. Dynamin-related proteins, in contrast, remodel other cellular membranes after binding to them via specific adaptor proteins. The mitochondrial fission protein Dnm1, for example, is recruited to yeast mitochondria by Mdv1, though how Dnm1 interacts with this adaptor protein is unclear.
Bui et al. identified several point mutations that prevented Dnm1 from localizing to mitochondria and supporting mitochondrial fission. The mutations were located in a conserved motif in the “Insert B” domain of Dnm1, a domain found in all dynamin-related proteins but not in dynamin itself, which instead contains a lipid-binding PH domain. Mutations in Dnm1’s Insert B domain inhibited the GTPase’s interaction with Mdv1. The interaction was rescued by suppressor mutations in Mdv1’s b-propeller domain, as was Dnm1’s mitochondrial recruitment and organelle fission.
The critical motif in yeast Dnm1 Insert B is well conserved in other fungi but is altered in the mammalian homologue, Drp1. But Mdv1 is also absent in mammals, where it is functionally replaced by several different mitochondrial adaptor proteins. Senior author Janet Shaw therefore thinks that Insert B sequences have co-evolved with their corresponding adaptors. She now wants to confirm the importance of the Insert B domain of mammalian Drp1 and to investigate whether it binds to different adaptors under different conditions.
Text by Ben Short