Dynamin-like Inhibitors

Dynamin-like inhibitors constitute a diverse class of small organic molecules designed to interfere with the activity of dynamin proteins and their closely related counterparts, such as dynamin-related proteins (DRPs). These compounds have garnered significant attention due to their pivotal role in regulating intracellular membrane dynamics, particularly in processes like endocytosis, vesicle trafficking, and mitochondrial fission. The central mechanism of action underlying dynamin-like inhibitors revolves around their ability to disrupt the GTPase activity and protein-protein interactions of these key cellular players.

At their core, dynamin-like proteins like dynamin, Mx, and DRPs share structural similarities characterized by a GTPase domain, middle domain, and GTPase effector domain (GED). Dynamin-like inhibitors often target the GTPase domain or other functionally critical regions. For example, compounds like Dynasore and Dyngo-4a specifically bind to the GTPase domain of dynamin, hampering its ability to hydrolyze GTP. This inhibition leads to the accumulation of dynamin in its GTP-bound state, which disrupts the coordination between dynamin and other factors necessary for vesicle scission, effectively halting endocytosis or other membrane remodeling processes. Additionally, some inhibitors, like MiTMAB, selectively bind to the pleckstrin homology (PH) domain of dynamin, interfering with its interactions with cellular membranes and impairing its membrane sculpting functions.Dynamin-like inhibitors represent valuable tools in cell biology research, aiding in the dissection of cellular processes reliant on membrane dynamics. They offer insights into the fundamental mechanisms governing membrane scission and fusion events, facilitating a deeper understanding of cell biology. Additionally, their applications extend beyond basic research, as they hold promise in modulating cellular processes in a controlled manner, which may have implications in various fields, including drug delivery and nanotechnology.