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@ARTICLE{Saller:275933,
author = {Saller, Benedikt S and Wöhrle, Svenja and Fischer, Larissa
and Dufossez, Clara and Ingerl, Isabella L and Kessler,
Susanne and Mateo-Tortola, Maria and Gorka, Oliver and
Lange, Felix and Cheng, Yurong and Neuwirt, Emilia and
Marada, Adinarayana and Koentges, Christoph and Urban,
Chiara and Aktories, Philipp and Reuther, Peter and Giese,
Sebastian and Kirschnek, Susanne and Mayer, Carolin and
Pilic, Johannes and Falquez-Medina, Hugo and Oelgeklaus,
Aline and Deepagan, Veerasikku Gopal and Shojaee, Farzaneh
and Zimmermann, Julia A and Weber, Damian and Tai, Yi-Heng
and Crois, Anna and Ciminski, Kevin and Peyronnet, Remi and
Brandenburg, Katharina S and Wu, Gang and Baumeister, Ralf
and Heimbucher, Thomas and Rizzi, Marta and Riedel, Dietmar
and Helmstädter, Martin and Buescher, Joerg and Neumann,
Konstantin and Misgeld, Thomas and Kerschensteiner, Martin
and Walentek, Peter and Kreutz, Clemens and Maurer, Ulrich
and Rambold, Angelika S and Vince, James E and Edlich, Frank
and Malli, Roland and Häcker, Georg and Kierdorf, Katrin
and Meisinger, Chris and Köttgen, Anna and Jakobs, Stefan
and Weber, Alexander N R and Schwemmle, Martin and Groß,
Christina J and Groß, Olaf},
title = {{A}cute suppression of mitochondrial {ATP} production
prevents apoptosis and provides an essential signal for
{NLRP}3 inflammasome activation.},
journal = {Immunity},
volume = {58},
number = {1},
issn = {1074-7613},
address = {[Cambridge, Mass.]},
publisher = {Cell Press},
reportid = {DZNE-2025-00155},
pages = {90 - 107.e11},
year = {2025},
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.},
keywords = {NLR Family, Pyrin Domain-Containing 3 Protein: metabolism /
Inflammasomes: metabolism / Mitochondria: metabolism /
Apoptosis / Adenosine Triphosphate: metabolism / Animals /
Mice / Oxidative Phosphorylation / Humans / Signal
Transduction / Mice, Inbred C57BL / Pyroptosis / ATP (Other)
/ NLRP3 (Other) / OXPHOS (Other) / apoptosis (Other) /
bioenergetics (Other) / cell death (Other) / chemical
biology (Other) / cytochrome c (Other) / inflammasome
(Other) / mitochondria (Other) / pyroptosis (Other) / NLR
Family, Pyrin Domain-Containing 3 Protein (NLM Chemicals) /
Inflammasomes (NLM Chemicals) / Adenosine Triphosphate (NLM
Chemicals) / Nlrp3 protein, mouse (NLM Chemicals)},
cin = {AG Misgeld},
ddc = {610},
cid = {I:(DE-2719)1110000-4},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39571574},
doi = {10.1016/j.immuni.2024.10.012},
url = {https://pub.dzne.de/record/275933},
}