The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
K+ regulates Ca2+ to drive inflammasome signaling: dynamic visualization of ion flux in live cells
Open accessAbstract
P2X7 purinergic receptor engagement with extracellular ATP induces transmembrane potassium and calcium flux resulting in assembly of the NLRP3 inflammasome in LPS-primed macrophages. The role of potassium and calcium in inflammasome regulation is not well understood, largely due to limitations in existing methods for interrogating potassium in real time. The use of KS6, a novel sensor for selective and sensitive dynamic visualization of intracellular potassium flux in live cells, multiplexed with the intracellular calcium sensor Fluo-4, revealed a coordinated relationship between potassium and calcium. Interestingly, the mitochondrial potassium pool was mobilized in a P2X7 signaling, and ATP dose-dependent manner, suggesting a role for mitochondrial sensing of cytosolic ion perturbation. Through treatment with extracellular potassium we found that potassium efflux was necessary to permit sustained calcium entry, but not transient calcium flux from intracellular stores. Further, intracellular calcium chelation with BAPTA-AM indicated that P2X7-induced potassium depletion was independent of calcium mobilization. This evidence suggests that both potassium efflux and calcium influx are necessary for mitochondrial reactive oxygen generation upstream of NLRP3 inflammasome assembly and pyroptotic cell death. We propose a model wherein potassium efflux is necessary for calcium influx, resulting in mitochondrial reactive oxygen generation to trigger the NLRP3 inflammasome.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“this has been shown to elicit activation of the NLRP3 inflammasome in LPS-stimulated macrophages, which causes secretion of IL-18 (but also of the pro-inflammatory cytokine IL-1β) and may thus promote maintenance and function of the epithelial barrier (Mariathasan et al., 2006; Sutterwala et al., 2014; 2006; Yaron et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Yaron et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708 · cited 3×
“Mitochondrial dysfunction and loss of mitochondrial membrane potential lead to a rapid increase in mROS production, which has been described to activate the inflammasome through the activity of thioredoxin-interacting protein (TXNIP).(16) In support of this mechanism, most known NLRP3-activating stimuli induce ROS gen…”
BackgroundMuñoz-Planillo, R., Kuffa, P., Martínez-Colón, G. J., Smith, B. L., Rajendiran, T. M., & Núñez, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.016 · Cited by 2,167
Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration
Pétrilli, V, Papin, S., Dostert, C., Mayor, A., Martinon, F., & Tschopp, J. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402195 · Cited by 1,445 · cited 3×
“Despite the proposed link between potassium efflux and mitochondrial signaling resulting in inflammasome assembly, this association had yet to be observed.(1,18,19,27) Further, there has been limited evidence regarding the relationship between calcium and potassium.”
BackgroundMethodThe calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
Lee, G., Subramanian, N., Kim, A. I., Aksentijevich, I. A., Goldbach‐Mansky, R. T., Sacks, D. B., Germain, R. N., Kastner, D. L., & Chae, J. J. (2012) · Nature · doi:10.1038/nature11588 · Cited by 1,077 · cited 1×
“A previous study has shown that intracellular calcium chelation with BAPTA-AM suppresses IL-1β processing and release upon ATP-induced inflammasome activation.(14) In agreement with this observation, we found that BAPTAAM significantly suppressed ATP-induced IL-1β processing and release as indicated by ELISA in J774A.”
Critical role for calcium mobilization in activation of the NLRP3 inflammasome
Murakami, T., Öckinger, J., Yu, J., Byles, V., McColl, A., Hofer, A. M., & Horng, T. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117765109 · Cited by 961 · cited 1×
“calcium response is indicative of the kinetics associated with rapid, endoplasmic reticulum-stored calcium ahead of plasma membrane-localized calcium entry from the extracellular environment.(26) Importantly, potassium flux occurred concurrently with the second phase of calcium influx, but was stable through the initi…”
BackgroundSyk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
Groß, O., Poeck, H., Bscheider, M., Dostert, C., Hannesschläger, N., Endres, S., Hartmann, G., Tardivel, A., Schweighoffer, E., Tybulewicz, V. L. J., et al. (2009) · Nature · doi:10.1038/nature07965 · Cited by 947
Flagged first, then by citations
Research works printed but not linked: 1
- Murakami T, Ockinger J, Yu J, Byles V . Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci USA 2012; 109: 11282–11287. · DOI
Cited by
Sorted by citations
Items 201–212 of 212
Assrawi, E. (2019) · theses.fr (ABES) · doi:10.70675/82f530d5z0154z474cz9746z470b6a42c9e0
Louvrier, C. (2019) · theses.fr (ABES) · doi:10.70675/ee57af23z15cdz4ec8zafebz9f9ac9f08220
Chirayath, T. W. (2023) · theses.fr (ABES) · doi:10.70675/5dbfa9f5zf8d1z4e51zaf01z277a9548aeeb
Ciblage de l'IL-1beta pour améliorer l'efficacité de la chimio-immunothérapie dans le cancer
Perrichet, A. (2024) · theses.fr (ABES) · doi:10.70675/b9026a2bzb830z46f0z8122z216dad542b24
Herring, M., Persson, A., Karlsson, R., Repsilber, D., Ejdebäck, M., Särndahl, E., Nikaein, N., & Kotlyar, O. (2026) · Scientific Reports · doi:10.1038/s41598-026-50936-x
Research on the NLRP3 Inflammasome in Microglia in PND Progress
王, 馨. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.1672730
Porcine coronavirus promotes NLRP3 inflammasome activation during virus-induced neuroinflammation
Zhou, Q., Shi, J., Qiu, R., Dai, R., Lan, Y., Zhou, J., Deng, X., He, W., & Li, Z. (2026) · mBio · doi:10.1128/mbio.01725-26
“Beyond its role in neuropathology, NLRP3 activation orchestrated a profound shift in cell fate and can be affected by indirect signals such as dysregulated ion flux, mitochon drial ROS production, and lysosomal destabilization (57–59).”
The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death
Xiao, N., Lu, Z., Cooper, D. K., & Chen, J. (2026) · Cellular and Molecular Immunology · doi:10.1038/s41423-026-01463-2 · Cited by 2
Phuong, M., Mahdi, A., Cai, D., Noah, K., Rijal, D., Kaul, R., Bhan, A., Yadav, S., Ariana, A., Hamra, R. E., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118037
Berghausen, J., Deniz, E., Wang, Z.-J., Schmidt, M. O., Ma, J., Creswell, K. M., Üren, A., Glasgow, E., Wellstein, A., & Brelidze, T. I. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113590
“Increased K + efflux the membrane and increases the driving force for Ca 2+ entry through calcium channels, thereby increasing the concentration of intracellular Ca 2+ —a major regulator of many oncogenic processes (66–68).”
Zhou, P., Ma, Y., Hou, C., Chen, C., & Deng, S. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1924945
Yu, S., Ren, X., Ding, Y., Xu, Y., Sun, M., Zhang, G., Zhang, B., Xing, Q., Guihua, S. O. N. G., & Wang, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1915398
Metadata
- Authors
- Yaron, J. R., Gangaraju, S., Rao, M. Y., Kong, X., Zhang, L., Su, F., Tian, Y., Glenn, H. L., & Meldrum, D. R.
- Affiliations
- Arizona State University (US)
- Corresponding author
- Meldrum, D R
- Venue
- Cell Death & Disease
- Published
- 2015-10-29
- Volume
- 6
- Issue
- 10
- Pages
- e1954-e1954
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5399176
- OpenAlex
- W2212334792
- Cited by
- 212
- References
- 44
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 20 · 2023: 25 · 2022: 21 · 2021: 22 · 2020: 25 · 2019: 18 · 2018: 23 · 2017: 14 · 2016: 11
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (P50HG002360)
- National Cancer Institute (U01CA164250)
- Common Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- P2X7 receptor, NLRP3 inflammasome, potassium efflux, calcium influx, Fluo-4, mitochondrial reactive oxygen species, pyroptosis, macrophages, LPS priming, extracellular ATP, BAPTA-AM
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Cell Line, Macrophages, Mitochondria, Models, Biological, Potassium, Reactive Oxygen Species, Calcium Signaling, Mice, Receptors, Purinergic P2X7, Inflammasomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
