TY  - JOUR
AU  - Saller, Benedikt S
AU  - Wöhrle, Svenja
AU  - Fischer, Larissa
AU  - Dufossez, Clara
AU  - Ingerl, Isabella L
AU  - Kessler, Susanne
AU  - Mateo-Tortola, Maria
AU  - Gorka, Oliver
AU  - Lange, Felix
AU  - Cheng, Yurong
AU  - Neuwirt, Emilia
AU  - Marada, Adinarayana
AU  - Koentges, Christoph
AU  - Urban, Chiara
AU  - Aktories, Philipp
AU  - Reuther, Peter
AU  - Giese, Sebastian
AU  - Kirschnek, Susanne
AU  - Mayer, Carolin
AU  - Pilic, Johannes
AU  - Falquez-Medina, Hugo
AU  - Oelgeklaus, Aline
AU  - Deepagan, Veerasikku Gopal
AU  - Shojaee, Farzaneh
AU  - Zimmermann, Julia A
AU  - Weber, Damian
AU  - Tai, Yi-Heng
AU  - Crois, Anna
AU  - Ciminski, Kevin
AU  - Peyronnet, Remi
AU  - Brandenburg, Katharina S
AU  - Wu, Gang
AU  - Baumeister, Ralf
AU  - Heimbucher, Thomas
AU  - Rizzi, Marta
AU  - Riedel, Dietmar
AU  - Helmstädter, Martin
AU  - Buescher, Joerg
AU  - Neumann, Konstantin
AU  - Misgeld, Thomas
AU  - Kerschensteiner, Martin
AU  - Walentek, Peter
AU  - Kreutz, Clemens
AU  - Maurer, Ulrich
AU  - Rambold, Angelika S
AU  - Vince, James E
AU  - Edlich, Frank
AU  - Malli, Roland
AU  - Häcker, Georg
AU  - Kierdorf, Katrin
AU  - Meisinger, Chris
AU  - Köttgen, Anna
AU  - Jakobs, Stefan
AU  - Weber, Alexander N R
AU  - Schwemmle, Martin
AU  - Groß, Christina J
AU  - Groß, Olaf
TI  - Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation.
JO  - Immunity
VL  - 58
IS  - 1
SN  - 1074-7613
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DZNE-2025-00155
SP  - 90 - 107.e11
PY  - 2025
AB  - 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.
KW  - NLR Family, Pyrin Domain-Containing 3 Protein: metabolism
KW  - Inflammasomes: metabolism
KW  - Mitochondria: metabolism
KW  - Apoptosis
KW  - Adenosine Triphosphate: metabolism
KW  - Animals
KW  - Mice
KW  - Oxidative Phosphorylation
KW  - Humans
KW  - Signal Transduction
KW  - Mice, Inbred C57BL
KW  - Pyroptosis
KW  - ATP (Other)
KW  - NLRP3 (Other)
KW  - OXPHOS (Other)
KW  - apoptosis (Other)
KW  - bioenergetics (Other)
KW  - cell death (Other)
KW  - chemical biology (Other)
KW  - cytochrome c (Other)
KW  - inflammasome (Other)
KW  - mitochondria (Other)
KW  - pyroptosis (Other)
KW  - NLR Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals)
KW  - Inflammasomes (NLM Chemicals)
KW  - Adenosine Triphosphate (NLM Chemicals)
KW  - Nlrp3 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39571574
DO  - DOI:10.1016/j.immuni.2024.10.012
UR  - https://pub.dzne.de/record/275933
ER  -