ESCRT puts its thumb on the nanoscale: Fixing tiny holes in endolysosomes

The ESCRT (endosomal complex required for transport) machinery remodels membranes to bud vesicles away from the cytoplasm. In addition to this classic role, ESCRTs are now understood to repair damage in the plasma membrane, nuclear envelope, and throughout the endolysosomal network. Wounds in endolysosomal membranes are caused by pathogens, particulates, and other chemical or metabolic stresses. Nanoscale damage in these membranes promotes activation and engagement of ESCRT proteins. A full understanding of damage signals, molecular sensing, and the mechanism of membrane repair is yet to be developed. Nevertheless, a triggering role for calcium and ESCRT-I in recruiting ESCRT-III machinery for membrane remodeling is a repeated theme in functional studies of this response. In our current understanding of the continuum of cellular responses to lipid bilayer damage, the ESCRT machinery is fast, sensitive, and deployed independently of other systems.