Abstract
In plants, metacaspases—cysteine proteases—have gained attention for their roles in programmed cell death (PCD). However, to date, their proteolytic activity has not been established as a direct executioner of PCD, analogous to caspases in animals. In this regard, the specific executioners of PCD remain to be identified in plants, leaving the process less well understood than in animals. More recently, metacaspases have also been recognized for their roles in cellular homeostasis. This perspective explores the pro-death and pro-survival roles of plant metacaspases in plant stress responses and development. Under abiotic stress conditions, such as heat, drought or high salinity, metacaspases help maintain protein homeostasis and mitigate damage by regulating processes like the unfolded protein response. In plant immunity, metacaspases have context-dependent pro-death or pro-survival roles. Pro-survival roles include cleavage and generation of immune peptides and regulating immune receptor stability as part of immunocondensates. They have also been shown to tightly regulate immunogenic cell death after pathogen attack, although their mode of action in this context remains elusive. Developmentally, metacaspases participate in key processes that involve PCD, like xylem differentiation and lateral root cap formation, where they help control cellular remodelling. Ultimately, metacaspases are emerging as multifunctional molecules crucial to cellular integrity, immunity, and development. Understanding the balance between cell death and survival pathways in plants is crucial, as it directly impacts crop resilience to environmental stresses and pathogens, ultimately influencing food security and our dependence on plant-based resources.
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Acknowledgements
We apologize to all the colleagues whose research could not be cited owing to space limitations. We thank Peter Vandenabeele, Jens Staal and Hamid Kashkar for enlightening discussions on metacaspases, paracaspases and caspases and to Joel Ayet and Elena Moreno for constructive discussion and feedback. Figures were created with the help of Biorender.com.
Funding
Research at CRAG was supported by grants PID2022-136922NB-I00 funded by MCIN/AEI/10.13039/501100011033 (to N.S.C.); N.R.-S. is the recipient of a predoctoral fellowship FPU19/03778 funded by MU (o Ministerio de Universidades). M.S.-G. is a recipient of the predoctoral fellowship HORIZON-MSCA-2021-COFUND rePLANT-GA101081581 Funded by the European Union. L.A. is a recipient of the postdoctoral fellowship HORIZON-MSCA-2021-PF-ImmunoZoneHubs-GA#101068121 Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the EUROPEAN RESEARCH EXECUTIVE AGENCY (REA). Neither the European Union nor the granting authority can be held responsible for them. rePLANT MSCA-COFUND programmes are cofunded by the Severo Ochoa Programme for Centres of Excellence in R&D CEX2019-000902-S funded by MCIN/AEI/10.13039/501100011033. The work was also supported by the Generalitat de Catalunya through 2021SGR00675 and the CERCA Programme.
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Conceptualization: MS-G (lead), NR-S (supporting), LA (lead), NSC (lead). Writing - original draft: MS-G, NR-S, LA, NSC. Writing – review and editing: MS-G, NR-S, LA, NSC. Supervision: NSC. Funding acquisition: NSC, LA.
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Salas-Gómez, M., Ruiz-Solaní, N., Armengot, L. et al. The role of plant metacaspases in cell death and survival. Cell Death Differ (2025). https://doi.org/10.1038/s41418-025-01555-y
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DOI: https://doi.org/10.1038/s41418-025-01555-y