The ESCRT Machinery: Remodeling, Repairing, and Sealing Membranes

Abstract

The ESCRT machinery is an evolutionarily conserved membrane remodeling complex that is used by the cell to perform reverse membrane scission in essential processes like protein degradation, cell division, and release of enveloped retroviruses. ESCRT-III, together with the AAA ATPase VPS4, harbors the main remodeling and scission function of the ESCRT machinery, whereas early-acting ESCRTs mainly contribute to protein sorting and ESCRT-III recruitment through association with upstream targeting factors. Here, we review recent advances in our understanding of the molecular mechanisms that underlie membrane constriction and scission by ESCRT-III and describe the involvement of this machinery in the sealing and repairing of damaged cellular membranes, a key function to preserve cellular viability and organellar function.

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

“…The first pathway utilizes the Endosomal Sorting Complex Required for Transport (ESCRT). This machinery contains up to 30 proteins which can be divided into four protein complexes: ESCRT-0, -I, -II, -III, and the associated ATPase Vps4 complex [ 34 , 35 , 36 , 37 ]. ESCRT-0 recognizes and sorts the ubiquitinated cargo proteins into the lipid domain [ 38 , 39 ].…”

Lysosomal dysfunction in diabetic cardiomyopathy

“…However, this can initiate ion leakage and pH changes within the lysosome, causing dysfunction of acidification and destabilization of lysosomal homeostasis (Ishida et al, 2013). Depending on the degree of the LMP, there are two types of responses that repair damaged lysosomes (Figure 1B): 1) Restoring limited membrane rupture, including endosomal sorting complex required for transport (ESCRT) machinery (Niekamp et al, 2022;Olmos, 2022), sphingomyelin scrambling (Niekamp et al, 2022), and phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway (Tan and Finkel, 2022); 2) Regenerating entire vesicles through autophagy (lysophagy and autophagy lysosome reformation ALR). (Nanayakkara et al, 2022).…”

Lgd regulates ESCRT-III complex accumulation at multivesicular endosomes to control intralumenal vesicle formation

“…The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in membrane remodeling events at numerous intracellular sites, including endosomes, lysosomes, autophagosomes, plasma membrane, endoplasmic reticulum, and the nuclear envelope ( Gatta and Carlton, 2019 ; Vietri et al. , 2020 ; Olmos, 2022 ). In particular, ESCRT-III complexes facilitate both membrane bending and scission, likely through their ability to form dynamic filaments that are capable of binding to lipid bilayers with high affinity, while simultaneously undergoing constriction ( Pfitzner et al.…”

“…, 2022 ). How the recruitment and dynamics of ESCRT-III complexes are regulated at these different sites remains poorly understood, but likely relies upon upstream components of the ESCRT machinery, as well as accessory factors that have been shown to interact with ESCRT-III subunits ( Olmos, 2022 ).…”

“…All exhibit structural similarities to one another, including the presence of multiple alpha helices, which have been shown to mediate homo- and heteropolymerization between individual subunits. In some cases, regulation of this assembly process has been suggested to rely on conformational changes that expose binding interfaces ( Olmos, 2022 ; Migliano et al ., 2022). As an example, inactive CHMP3 appears to exist in a closed state, where five of its alpha helices are packed against one another to prevent polymerization ( Muziol et al.…”