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Comment
. 2025 Jan 14;58(1):5-7.
doi: 10.1016/j.immuni.2024.12.007.

Mitochondria and NLRP3: To die or inflame

Shuangshuang Yang  1 , Guannan Huang  1 , Jenny P-Y Ting  2
Affiliations
Comment

Mitochondria and NLRP3: To die or inflame

Shuangshuang Yang et al. Immunity. .

Abstract

Mitochondria play critical roles in intrinsic apoptosis and NLRP3 inflammasome activation, but how these processes are interconnected remains unclear. In this issue of Immunity, Saller et al. unveiled the complexity of NLRP3 activators, highlighting mitochondria's roles in switching apoptosis to NLRP3 inflammasome activation.

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Conflict of interest statement

Declaration of interests J.P.-Y.T. is a co-founder of IMMvention Therapeutix.

Figures

Figure 1.
Figure 1.
“Two activation signals” model proposed in the current study. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome requires two activation signals: one mitochondrial signal and an additional signal (e.g., resiquimod, gardiquimod or Yoda-1) that is not yet defined but involves. Reduced ATP production or oxidative phosphorylation (OXPHOS) inhibition accounts for the first/mitochondrial signal, triggering cristae closure and trapping cytochrome c (cyt c) within the lumen. Limited cyt c release further dampens apoptosome formation and subsequent intrinsic apoptosis while enabling pyroptosis. Apaf-1 = Apoptotic protease activating factor 1. IL-1β = interleukin-1β. ADP = Adenosine Diphosphate. ATP = Adenosine Triphosphate. I, II, III, IV, and V refer to electron transport chain complex I through V. Illustration created in Biorender.
See this image and copyright information in PMC

Comment on

  • Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation.
    Saller BS, Wöhrle S, Fischer L, Dufossez C, Ingerl IL, Kessler S, Mateo-Tortola M, Gorka O, Lange F, Cheng Y, Neuwirt E, Marada A, Koentges C, Urban C, Aktories P, Reuther P, Giese S, Kirschnek S, Mayer C, Pilic J, Falquez-Medina H, Oelgeklaus A, Deepagan VG, Shojaee F, Zimmermann JA, Weber D, Tai YH, Crois A, Ciminski K, Peyronnet R, Brandenburg KS, Wu G, Baumeister R, Heimbucher T, Rizzi M, Riedel D, Helmstädter M, Buescher J, Neumann K, Misgeld T, Kerschensteiner M, Walentek P, Kreutz C, Maurer U, Rambold AS, Vince JE, Edlich F, Malli R, Häcker G, Kierdorf K, Meisinger C, Köttgen A, Jakobs S, Weber ANR, Schwemmle M, Groß CJ, Groß O. Saller BS, et al. Immunity. 2025 Jan 14;58(1):90-107.e11. doi: 10.1016/j.immuni.2024.10.012. Epub 2024 Nov 20. Immunity. 2025. PMID: 39571574

References

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