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. 2023 Oct 16;39(10-12):708–727. doi: 10.1089/ars.2022.0209

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© Sergio Rius-Pérez et al., 2023; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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FIG. 5. — Regulation of pyroptosis by mtROS. DAMPs and PAMPs activate the NLRP3 inflammasome, which triggers caspase-1-dependent release of IL-1β and IL-18 and cleavages gasdermin. Cleaved gasdermins oligomerizes and inserts into the plasma membrane causing membrane permeabilization and cell killing. Pyroptosis can also be induced by an inflammasome independent pathway through caspase-11, caspase-4, and/or caspase-5. The ER stress response and mitochondrial dysfunction promotes mtROS production. The mtROS enhances NLRP3 inflammasome activation and oxidizes gasdermin D, which enhances its cleavage by caspase-1. Mitofusin 2 and PRX3 lowered mtROS and suppressed NLRP3 activation and pyroptosis. DAMPs, damage-associated molecular patterns; ER, endoplasmic reticulum; IL, interleukin; PAMPs, pathogen-associated molecular patterns.