Mitochondrial damage activates the NLRP10 inflammasome

Tomasz Próchnicki; Matilde B. Vasconcelos; Kim S. Robinson; Matthew S.J. Mangan; Dennis De Graaf; Kateryna Shkarina; Marta Lovotti; Lena Standke; Romina Kaiser; Rainer Stahl; Fraser G. Duthie; Maximilian Rothe; Kateryna Antonova; Lea Marie Jenster; Zhi Heng Lau; Sarah Rösing; Nora Mirza; Clarissa Gottschild; Dagmar Wachten; Claudia Günther; Thomas A. Kufer; Florian I. Schmidt; Franklin L. Zhong; Eicke Latz

doi:10.1038/s41590-023-01451-y

Mitochondrial damage activates the NLRP10 inflammasome

Tomasz Próchnicki, Matilde B. Vasconcelos, Kim S. Robinson, Matthew S.J. Mangan, Dennis De Graaf, Kateryna Shkarina, Marta Lovotti, Lena Standke, Romina Kaiser, Rainer Stahl, Fraser G. Duthie, Maximilian Rothe, Kateryna Antonova, Lea Marie Jenster, Zhi Heng Lau, Sarah Rösing, Nora Mirza, Clarissa Gottschild, Dagmar Wachten, Claudia GüntherThomas A. Kufer, Florian I. Schmidt, Franklin L. Zhong, Eicke Latz^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Upon detecting pathogens or cell stress, several NOD-like receptors (NLRs) form inflammasome complexes with the adapter ASC and caspase-1, inducing gasdermin D (GSDMD)-dependent cell death and maturation and release of IL-1β and IL-18. The triggers and activation mechanisms of several inflammasome-forming sensors are not well understood. Here we show that mitochondrial damage activates the NLRP10 inflammasome, leading to ASC speck formation and caspase-1-dependent cytokine release. While the AIM2 inflammasome can also sense mitochondrial demise by detecting mitochondrial DNA (mtDNA) in the cytosol, NLRP10 monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles. NLRP10 is highly expressed in differentiated human keratinocytes, in which it can also assemble an inflammasome. Our study shows that this inflammasome surveils mitochondrial integrity. These findings might also lead to a better understanding of mitochondria-linked inflammatory diseases.

Original language	English
Pages (from-to)	595-603
Number of pages	9
Journal	Nature Immunology
Volume	24
Issue number	4
DOIs	https://doi.org/10.1038/s41590-023-01451-y
Publication status	Published - Apr 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41590-023-01451-y

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Próchnicki, T., Vasconcelos, M. B., Robinson, K. S., Mangan, M. S. J., De Graaf, D., Shkarina, K., Lovotti, M., Standke, L., Kaiser, R., Stahl, R., Duthie, F. G., Rothe, M., Antonova, K., Jenster, L. M., Lau, Z. H., Rösing, S., Mirza, N., Gottschild, C., Wachten, D., ... Latz, E. (2023). Mitochondrial damage activates the NLRP10 inflammasome. Nature Immunology, 24(4), 595-603. https://doi.org/10.1038/s41590-023-01451-y

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title = "Mitochondrial damage activates the NLRP10 inflammasome",

abstract = "Upon detecting pathogens or cell stress, several NOD-like receptors (NLRs) form inflammasome complexes with the adapter ASC and caspase-1, inducing gasdermin D (GSDMD)-dependent cell death and maturation and release of IL-1β and IL-18. The triggers and activation mechanisms of several inflammasome-forming sensors are not well understood. Here we show that mitochondrial damage activates the NLRP10 inflammasome, leading to ASC speck formation and caspase-1-dependent cytokine release. While the AIM2 inflammasome can also sense mitochondrial demise by detecting mitochondrial DNA (mtDNA) in the cytosol, NLRP10 monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles. NLRP10 is highly expressed in differentiated human keratinocytes, in which it can also assemble an inflammasome. Our study shows that this inflammasome surveils mitochondrial integrity. These findings might also lead to a better understanding of mitochondria-linked inflammatory diseases.",

author = "Tomasz Pr{\'o}chnicki and Vasconcelos, {Matilde B.} and Robinson, {Kim S.} and Mangan, {Matthew S.J.} and {De Graaf}, Dennis and Kateryna Shkarina and Marta Lovotti and Lena Standke and Romina Kaiser and Rainer Stahl and Duthie, {Fraser G.} and Maximilian Rothe and Kateryna Antonova and Jenster, {Lea Marie} and Lau, {Zhi Heng} and Sarah R{\"o}sing and Nora Mirza and Clarissa Gottschild and Dagmar Wachten and Claudia G{\"u}nther and Kufer, {Thomas A.} and Schmidt, {Florian I.} and Zhong, {Franklin L.} and Eicke Latz",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = apr,

doi = "10.1038/s41590-023-01451-y",

language = "English",

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Próchnicki, T, Vasconcelos, MB, Robinson, KS, Mangan, MSJ, De Graaf, D, Shkarina, K, Lovotti, M, Standke, L, Kaiser, R, Stahl, R, Duthie, FG, Rothe, M, Antonova, K, Jenster, LM, Lau, ZH, Rösing, S, Mirza, N, Gottschild, C, Wachten, D, Günther, C, Kufer, TA, Schmidt, FI, Zhong, FL & Latz, E 2023, 'Mitochondrial damage activates the NLRP10 inflammasome', Nature Immunology, vol. 24, no. 4, pp. 595-603. https://doi.org/10.1038/s41590-023-01451-y

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AU - Próchnicki, Tomasz

AU - Vasconcelos, Matilde B.

AU - Robinson, Kim S.

AU - Mangan, Matthew S.J.

AU - De Graaf, Dennis

AU - Shkarina, Kateryna

AU - Lovotti, Marta

AU - Standke, Lena

AU - Kaiser, Romina

AU - Stahl, Rainer

AU - Duthie, Fraser G.

AU - Rothe, Maximilian

AU - Antonova, Kateryna

AU - Jenster, Lea Marie

AU - Lau, Zhi Heng

AU - Rösing, Sarah

AU - Mirza, Nora

AU - Gottschild, Clarissa

AU - Wachten, Dagmar

AU - Günther, Claudia

AU - Kufer, Thomas A.

AU - Schmidt, Florian I.

AU - Zhong, Franklin L.

AU - Latz, Eicke

PY - 2023/4

Y1 - 2023/4

N2 - Upon detecting pathogens or cell stress, several NOD-like receptors (NLRs) form inflammasome complexes with the adapter ASC and caspase-1, inducing gasdermin D (GSDMD)-dependent cell death and maturation and release of IL-1β and IL-18. The triggers and activation mechanisms of several inflammasome-forming sensors are not well understood. Here we show that mitochondrial damage activates the NLRP10 inflammasome, leading to ASC speck formation and caspase-1-dependent cytokine release. While the AIM2 inflammasome can also sense mitochondrial demise by detecting mitochondrial DNA (mtDNA) in the cytosol, NLRP10 monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles. NLRP10 is highly expressed in differentiated human keratinocytes, in which it can also assemble an inflammasome. Our study shows that this inflammasome surveils mitochondrial integrity. These findings might also lead to a better understanding of mitochondria-linked inflammatory diseases.

AB - Upon detecting pathogens or cell stress, several NOD-like receptors (NLRs) form inflammasome complexes with the adapter ASC and caspase-1, inducing gasdermin D (GSDMD)-dependent cell death and maturation and release of IL-1β and IL-18. The triggers and activation mechanisms of several inflammasome-forming sensors are not well understood. Here we show that mitochondrial damage activates the NLRP10 inflammasome, leading to ASC speck formation and caspase-1-dependent cytokine release. While the AIM2 inflammasome can also sense mitochondrial demise by detecting mitochondrial DNA (mtDNA) in the cytosol, NLRP10 monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles. NLRP10 is highly expressed in differentiated human keratinocytes, in which it can also assemble an inflammasome. Our study shows that this inflammasome surveils mitochondrial integrity. These findings might also lead to a better understanding of mitochondria-linked inflammatory diseases.

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JF - Nature Immunology

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Mitochondrial damage activates the NLRP10 inflammasome

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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