Pore-forming proteins as drivers of membrane permeabilization in cell death pathways
- Author
- Peter Vandenabeele (UGent) , Geert Bultynck and Savvas Savvides (UGent)
- Organization
- Project
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- MOlecular mechanisms of cellular DEath and Life decisions in Inflammation, Degeneration and Infection
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Factors that determine RIPK1-dependent necroptosis
- Investigating the role of ferroptosis in acute liver injury and multiple sclerosis with newly developed chemical tool compounds
- Mechanisms of ferroptosis mediated immunoregulation
- Autophagy in inflammation and inflammatory disorders (ATLANTIS), from basic insights to experimental therapy
- Cell death activity regulation in inflammation and cancer
- Towards the structural and molecular basis of pro-inflammatory signalling assemblies mediated by IL-23 and IL-12
- An integrated approach to unravel eosinophil function in chronic eosinophilic disorders
- Thymic reprogramming: The role of Death Receptor 3 (DR3)
- Unraveling the structural and functional roles of THEMIS proteins in T cell and B cell development and inflammation
- Abstract
- Regulated cell death (RCD) relies on activation and recruitment of pore-forming proteins (PFPs) that function as executioners of specific cell death pathways: apoptosis regulator BAX (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-2-related ovarian killer protein (BOK) for apoptosis, gasdermins (GSDMs) for pyroptosis and mixed lineage kinase domain-like protein (MLKL) for necroptosis. Inactive precursors of PFPs are converted into pore-forming entities through activation, membrane recruitment, membrane insertion and oligomerization. These mechanisms involve protein-protein and protein-lipid interactions, proteolytic processing and phosphorylation. In this Review, we discuss the structural rearrangements incurred by RCD-related PFPs and describe the mechanisms that manifest conversion from autoinhibited to membrane-embedded molecular states. We further discuss the formation and maturation of membrane pores formed by BAX/BAK/BOK, GSDMs and MLKL, leading to diverse pore architectures. Lastly, we highlight commonalities and differences of PFP mechanisms involving BAX/BAK/BOK, GSDMs and MLKL and conclude with a discussion on how, in a population of challenged cells, the coexistence of cell death modalities may have profound physiological and pathophysiological implications.
- Keywords
- MIXED LINEAGE KINASE, GASDERMIN D, MEDIATES NECROPTOSIS, APOPTOTIC ACTIVITY, PROAPOPTOTIC BAX, BH3 DOMAIN, MLKL, ACTIVATION, FAMILY, MITOCHONDRIA
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GTKY2WYTPQHH59VBV4GBMBHW
- MLA
- Vandenabeele, Peter, et al. “Pore-Forming Proteins as Drivers of Membrane Permeabilization in Cell Death Pathways.” NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 24, no. 5, 2023, pp. 312–33, doi:10.1038/s41580-022-00564-w.
- APA
- Vandenabeele, P., Bultynck, G., & Savvides, S. (2023). Pore-forming proteins as drivers of membrane permeabilization in cell death pathways. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 24(5), 312–333. https://doi.org/10.1038/s41580-022-00564-w
- Chicago author-date
- Vandenabeele, Peter, Geert Bultynck, and Savvas Savvides. 2023. “Pore-Forming Proteins as Drivers of Membrane Permeabilization in Cell Death Pathways.” NATURE REVIEWS MOLECULAR CELL BIOLOGY 24 (5): 312–33. https://doi.org/10.1038/s41580-022-00564-w.
- Chicago author-date (all authors)
- Vandenabeele, Peter, Geert Bultynck, and Savvas Savvides. 2023. “Pore-Forming Proteins as Drivers of Membrane Permeabilization in Cell Death Pathways.” NATURE REVIEWS MOLECULAR CELL BIOLOGY 24 (5): 312–333. doi:10.1038/s41580-022-00564-w.
- Vancouver
- 1.Vandenabeele P, Bultynck G, Savvides S. Pore-forming proteins as drivers of membrane permeabilization in cell death pathways. NATURE REVIEWS MOLECULAR CELL BIOLOGY. 2023;24(5):312–33.
- IEEE
- [1]P. Vandenabeele, G. Bultynck, and S. Savvides, “Pore-forming proteins as drivers of membrane permeabilization in cell death pathways,” NATURE REVIEWS MOLECULAR CELL BIOLOGY, vol. 24, no. 5, pp. 312–333, 2023.
@article{01GTKY2WYTPQHH59VBV4GBMBHW,
abstract = {{Regulated cell death (RCD) relies on activation and recruitment of pore-forming proteins (PFPs) that function as executioners of specific cell death pathways: apoptosis regulator BAX (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-2-related ovarian killer protein (BOK) for apoptosis, gasdermins (GSDMs) for pyroptosis and mixed lineage kinase domain-like protein (MLKL) for necroptosis. Inactive precursors of PFPs are converted into pore-forming entities through activation, membrane recruitment, membrane insertion and oligomerization. These mechanisms involve protein-protein and protein-lipid interactions, proteolytic processing and phosphorylation. In this Review, we discuss the structural rearrangements incurred by RCD-related PFPs and describe the mechanisms that manifest conversion from autoinhibited to membrane-embedded molecular states. We further discuss the formation and maturation of membrane pores formed by BAX/BAK/BOK, GSDMs and MLKL, leading to diverse pore architectures. Lastly, we highlight commonalities and differences of PFP mechanisms involving BAX/BAK/BOK, GSDMs and MLKL and conclude with a discussion on how, in a population of challenged cells, the coexistence of cell death modalities may have profound physiological and pathophysiological implications.}},
author = {{Vandenabeele, Peter and Bultynck, Geert and Savvides, Savvas}},
issn = {{1471-0072}},
journal = {{NATURE REVIEWS MOLECULAR CELL BIOLOGY}},
keywords = {{MIXED LINEAGE KINASE,GASDERMIN D,MEDIATES NECROPTOSIS,APOPTOTIC ACTIVITY,PROAPOPTOTIC BAX,BH3 DOMAIN,MLKL,ACTIVATION,FAMILY,MITOCHONDRIA}},
language = {{eng}},
number = {{5}},
pages = {{312--333}},
title = {{Pore-forming proteins as drivers of membrane permeabilization in cell death pathways}},
url = {{http://doi.org/10.1038/s41580-022-00564-w}},
volume = {{24}},
year = {{2023}},
}
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