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ESCRT-III function in membrane fission and repair

Nature Reviews Molecular Cell Biology (2025)Cite this article

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Abstract

The endosomal sorting complex required for transport (ESCRT) machinery is an evolutionarily conserved multisubunit protein complex that remodels cellular membranes. Beyond its classical role in endosomal sorting, the ESCRT machinery has been implicated in an ever-growing number of functions, including viral budding, cytokinesis, autophagy, extracellular vesicle release, pruning of synaptic processes and the repair and closure of holes in cellular membranes. Membrane remodelling functions are typically ascribed to the ESCRT-III subcomplex. In this Review, we discuss recent mechanistic and structural insights into how these proteins assemble and are remodelled to achieve membrane severing. We focus particularly on how ESCRT-III is engaged at different subcellular compartments during both interphase and mitosis to repair and remodel membranes.

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Fig. 1: The ESCRT membrane remodelling machinery.
Fig. 2: Models of ESCRT-III-mediated membrane fission.
Fig. 3: ESCRT activity during membrane repair.
Fig. 4: ESCRT-III roles in autophagy.
Fig. 5: Regulation of ESCRT-III activity during cell division.

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Acknowledgements

J.G.C. is a Wellcome Trust Senior Research Fellow (grant no. 224484/Z/21/Z) and is supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (grant no. CC1002), the UK Medical Research Council (grant no. CC1002) and the Wellcome Trust (grant no. CC1002). M.B. is supported by an EMBO Postdoctoral Fellowship (grant no. ALTF 754-2023) and a Marie Skłodowska-Curie Actions via Horizon Europe Fellowship, underwritten through the EPSRC Horizon Europe Guarantee scheme. This research was funded in whole, or in part, by the Wellcome Trust (grant no. 224484/Z/21/Z, CC1002). For the purpose of Open Access, the authors have applied a Creative Commons Attribution (CC BY) public copyright licence to any Author Accepted Manuscript version arising from this submission.

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Authors and Affiliations

  1. Organelle Dynamics Laboratory, The Francis Crick Institute, London, UK

    M. Burigotto & J. G. Carlton

  2. School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK

    M. Burigotto & J. G. Carlton

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  1. M. Burigotto
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Supplementary information

Glossary

Coarse-grained simulations

Modelling techniques that simplify complex systems by grouping atoms or molecules into larger units (called beads), enabling the study of larger assemblies and longer timescales.

Laminopathies

A group of rare genetic disorders caused by mutations in genes encoding nuclear lamina protein, leading to abnormalities in nuclear shape and structure and resulting in conditions such as progeria syndromes and muscular dystrophies.

Midbody

A transient, protein-rich structure that assembles at the intercellular bridge during cytokinesis in mammalian cells.

Open mitosis

A type of cell division in higher eukaryotes where the nuclear envelope completely breaks down to allow chromosome segregation.

Stochastic optical reconstruction microscopy

A super-resolution imaging technique that uses the random switching of fluorescent molecules on and off to reconstruct highly detailed images beyond the diffraction limit.

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Burigotto, M., Carlton, J.G. ESCRT-III function in membrane fission and repair. Nat Rev Mol Cell Biol (2025). https://doi.org/10.1038/s41580-025-00909-1

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