Journal Article

DZNE-2025-00155

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation.

Saller, B. S. ; Wöhrle, S. ; Fischer, L.Extern* ; Dufossez, C. ; Ingerl, I. L. ; 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, V. G. ; Shojaee, F. ; Zimmermann, J. A. ; Weber, D. ; Tai, Y.-H. ; Crois, A. ; Ciminski, K. ; Peyronnet, R. ; Brandenburg, K. S. ; Wu, G. ; Baumeister, R. ; Heimbucher, T. ; Rizzi, M. ; Riedel, D. ; Helmstädter, M. ; Buescher, J. ; Neumann, K. ; Misgeld, T.DZNE* ; Kerschensteiner, M. ; Walentek, P. ; Kreutz, C. ; Maurer, U. ; Rambold, A. S. ; Vince, J. E. ; Edlich, F. ; Malli, R. ; Häcker, G. ; Kierdorf, K. ; Meisinger, C. ; Köttgen, A. ; Jakobs, S. ; Weber, A. N. R. ; Schwemmle, M. ; Groß, C. J. ; Groß, O.

2025
Cell Press [Cambridge, Mass.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.immuni.2024.10.012

Abstract: How mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome c. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.

Keyword(s): NLR Family, Pyrin Domain-Containing 3 Protein: metabolism (MeSH) ; Inflammasomes: metabolism (MeSH) ; Mitochondria: metabolism (MeSH) ; Apoptosis (MeSH) ; Adenosine Triphosphate: metabolism (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Oxidative Phosphorylation (MeSH) ; Humans (MeSH) ; Signal Transduction (MeSH) ; Mice, Inbred C57BL (MeSH) ; Pyroptosis (MeSH) ; ATP ; NLRP3 ; OXPHOS ; apoptosis ; bioenergetics ; cell death ; chemical biology ; cytochrome c ; inflammasome ; mitochondria ; pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammasomes ; Adenosine Triphosphate ; Nlrp3 protein, mouse

---

Contributing Institute(s):

1. Neuronal Cell Biology (AG Misgeld)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---