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000275933 0247_ $$2doi$$a10.1016/j.immuni.2024.10.012
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000275933 037__ $$aDZNE-2025-00155
000275933 041__ $$aEnglish
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000275933 1001_ $$aSaller, Benedikt S$$b0
000275933 245__ $$aAcute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation.
000275933 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000275933 520__ $$aHow mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome c. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.
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000275933 650_7 $$2Other$$aATP
000275933 650_7 $$2Other$$aNLRP3
000275933 650_7 $$2Other$$aOXPHOS
000275933 650_7 $$2Other$$aapoptosis
000275933 650_7 $$2Other$$abioenergetics
000275933 650_7 $$2Other$$acell death
000275933 650_7 $$2Other$$achemical biology
000275933 650_7 $$2Other$$acytochrome c
000275933 650_7 $$2Other$$ainflammasome
000275933 650_7 $$2Other$$amitochondria
000275933 650_7 $$2Other$$apyroptosis
000275933 650_7 $$2NLM Chemicals$$aNLR Family, Pyrin Domain-Containing 3 Protein
000275933 650_7 $$2NLM Chemicals$$aInflammasomes
000275933 650_7 $$08L70Q75FXE$$2NLM Chemicals$$aAdenosine Triphosphate
000275933 650_7 $$2NLM Chemicals$$aNlrp3 protein, mouse
000275933 650_2 $$2MeSH$$aNLR Family, Pyrin Domain-Containing 3 Protein: metabolism
000275933 650_2 $$2MeSH$$aInflammasomes: metabolism
000275933 650_2 $$2MeSH$$aMitochondria: metabolism
000275933 650_2 $$2MeSH$$aApoptosis
000275933 650_2 $$2MeSH$$aAdenosine Triphosphate: metabolism
000275933 650_2 $$2MeSH$$aAnimals
000275933 650_2 $$2MeSH$$aMice
000275933 650_2 $$2MeSH$$aOxidative Phosphorylation
000275933 650_2 $$2MeSH$$aHumans
000275933 650_2 $$2MeSH$$aSignal Transduction
000275933 650_2 $$2MeSH$$aMice, Inbred C57BL
000275933 650_2 $$2MeSH$$aPyroptosis
000275933 7001_ $$aWöhrle, Svenja$$b1
000275933 7001_ $$0P:(DE-2719)9002356$$aFischer, Larissa$$b2$$udzne
000275933 7001_ $$aDufossez, Clara$$b3
000275933 7001_ $$aIngerl, Isabella L$$b4
000275933 7001_ $$aKessler, Susanne$$b5
000275933 7001_ $$aMateo-Tortola, Maria$$b6
000275933 7001_ $$aGorka, Oliver$$b7
000275933 7001_ $$aLange, Felix$$b8
000275933 7001_ $$aCheng, Yurong$$b9
000275933 7001_ $$aNeuwirt, Emilia$$b10
000275933 7001_ $$aMarada, Adinarayana$$b11
000275933 7001_ $$aKoentges, Christoph$$b12
000275933 7001_ $$aUrban, Chiara$$b13
000275933 7001_ $$aAktories, Philipp$$b14
000275933 7001_ $$aReuther, Peter$$b15
000275933 7001_ $$aGiese, Sebastian$$b16
000275933 7001_ $$aKirschnek, Susanne$$b17
000275933 7001_ $$aMayer, Carolin$$b18
000275933 7001_ $$aPilic, Johannes$$b19
000275933 7001_ $$aFalquez-Medina, Hugo$$b20
000275933 7001_ $$aOelgeklaus, Aline$$b21
000275933 7001_ $$aDeepagan, Veerasikku Gopal$$b22
000275933 7001_ $$aShojaee, Farzaneh$$b23
000275933 7001_ $$aZimmermann, Julia A$$b24
000275933 7001_ $$aWeber, Damian$$b25
000275933 7001_ $$aTai, Yi-Heng$$b26
000275933 7001_ $$aCrois, Anna$$b27
000275933 7001_ $$aCiminski, Kevin$$b28
000275933 7001_ $$aPeyronnet, Remi$$b29
000275933 7001_ $$aBrandenburg, Katharina S$$b30
000275933 7001_ $$aWu, Gang$$b31
000275933 7001_ $$aBaumeister, Ralf$$b32
000275933 7001_ $$aHeimbucher, Thomas$$b33
000275933 7001_ $$aRizzi, Marta$$b34
000275933 7001_ $$aRiedel, Dietmar$$b35
000275933 7001_ $$aHelmstädter, Martin$$b36
000275933 7001_ $$aBuescher, Joerg$$b37
000275933 7001_ $$aNeumann, Konstantin$$b38
000275933 7001_ $$0P:(DE-2719)2810727$$aMisgeld, Thomas$$b39$$udzne
000275933 7001_ $$aKerschensteiner, Martin$$b40
000275933 7001_ $$aWalentek, Peter$$b41
000275933 7001_ $$aKreutz, Clemens$$b42
000275933 7001_ $$aMaurer, Ulrich$$b43
000275933 7001_ $$aRambold, Angelika S$$b44
000275933 7001_ $$aVince, James E$$b45
000275933 7001_ $$aEdlich, Frank$$b46
000275933 7001_ $$aMalli, Roland$$b47
000275933 7001_ $$aHäcker, Georg$$b48
000275933 7001_ $$aKierdorf, Katrin$$b49
000275933 7001_ $$aMeisinger, Chris$$b50
000275933 7001_ $$aKöttgen, Anna$$b51
000275933 7001_ $$aJakobs, Stefan$$b52
000275933 7001_ $$aWeber, Alexander N R$$b53
000275933 7001_ $$aSchwemmle, Martin$$b54
000275933 7001_ $$aGroß, Christina J$$b55
000275933 7001_ $$aGroß, Olaf$$b56
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