Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming
The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting in caspase-1-dependent secretion of the proinflammatory cytokines IL-1β and IL-18. Canonical NLRP3 inflammasome activation is a two-step process requiring both priming and activation signals. During inflammaso...
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| Veröffentlicht in: | The Journal of immunology (1950) 2018-05, Vol.200 (9), p.3047-3052 |
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| container_issue | 9 |
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| container_title | The Journal of immunology (1950) |
| container_volume | 200 |
| creator | Elliott, Eric I Miller, Alexis N Banoth, Balaji Iyer, Shankar S Stotland, Aleksandr Weiss, Jerrold P Gottlieb, Roberta A Sutterwala, Fayyaz S Cassel, Suzanne L |
| description | The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting in caspase-1-dependent secretion of the proinflammatory cytokines IL-1β and IL-18. Canonical NLRP3 inflammasome activation is a two-step process requiring both priming and activation signals. During inflammasome activation, NLRP3 associates with mitochondria; however, the role for this interaction is unclear. In this article, we show that mouse NLRP3 and caspase-1 independently interact with the mitochondrial lipid cardiolipin, which is externalized to the outer mitochondrial membrane at priming in response to reactive oxygen species. An NLRP3 activation signal is then required for the calcium-dependent association of the adaptor molecule ASC with NLRP3 on the mitochondrial surface, resulting in inflammasome complex assembly and activation. These findings demonstrate a novel lipid interaction for caspase-1 and identify a role for mitochondria as supramolecular organizing centers in the assembly and activation of the NLRP3 inflammasome. |
| doi_str_mv | 10.4049/jimmunol.1701723 |
| format | Article |
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Canonical NLRP3 inflammasome activation is a two-step process requiring both priming and activation signals. During inflammasome activation, NLRP3 associates with mitochondria; however, the role for this interaction is unclear. In this article, we show that mouse NLRP3 and caspase-1 independently interact with the mitochondrial lipid cardiolipin, which is externalized to the outer mitochondrial membrane at priming in response to reactive oxygen species. An NLRP3 activation signal is then required for the calcium-dependent association of the adaptor molecule ASC with NLRP3 on the mitochondrial surface, resulting in inflammasome complex assembly and activation. These findings demonstrate a novel lipid interaction for caspase-1 and identify a role for mitochondria as supramolecular organizing centers in the assembly and activation of the NLRP3 inflammasome.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1701723</identifier><identifier>PMID: 29602772</identifier><language>eng</language><publisher>United States: American Association of Immunologists</publisher><subject>Activation ; Animals ; Calcium ; Cardiolipin ; Cardiolipins - immunology ; Cardiolipins - metabolism ; Caspase ; Caspase 1 - immunology ; Caspase 1 - metabolism ; Caspase-1 ; Inflammasomes ; Inflammasomes - immunology ; Inflammasomes - metabolism ; Inflammation ; Interleukin 18 ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria ; Mitochondria - immunology ; Mitochondria - metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein - immunology ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Reactive oxygen species ; Secretion</subject><ispartof>The Journal of immunology (1950), 2018-05, Vol.200 (9), p.3047-3052</ispartof><rights>Copyright © 2018 by The American Association of Immunologists, Inc.</rights><rights>Copyright American Association of Immunologists May 1, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-c9cd7ff934976ab1fbac31a43152900bfcb699b7a01ec98e9866e7c50e3d3aaa3</citedby><cites>FETCH-LOGICAL-c416t-c9cd7ff934976ab1fbac31a43152900bfcb699b7a01ec98e9866e7c50e3d3aaa3</cites><orcidid>0000-0003-1476-4485 ; 0000-0003-4794-1097 ; 0000-0002-1432-006X ; 0000-0002-7467-2198 ; 0000-0003-0630-3478 ; 0000-0002-5384-2274</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29602772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elliott, Eric I</creatorcontrib><creatorcontrib>Miller, Alexis N</creatorcontrib><creatorcontrib>Banoth, Balaji</creatorcontrib><creatorcontrib>Iyer, Shankar S</creatorcontrib><creatorcontrib>Stotland, Aleksandr</creatorcontrib><creatorcontrib>Weiss, Jerrold P</creatorcontrib><creatorcontrib>Gottlieb, Roberta A</creatorcontrib><creatorcontrib>Sutterwala, Fayyaz S</creatorcontrib><creatorcontrib>Cassel, Suzanne L</creatorcontrib><title>Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting in caspase-1-dependent secretion of the proinflammatory cytokines IL-1β and IL-18. 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These findings demonstrate a novel lipid interaction for caspase-1 and identify a role for mitochondria as supramolecular organizing centers in the assembly and activation of the NLRP3 inflammasome.</description><subject>Activation</subject><subject>Animals</subject><subject>Calcium</subject><subject>Cardiolipin</subject><subject>Cardiolipins - immunology</subject><subject>Cardiolipins - metabolism</subject><subject>Caspase</subject><subject>Caspase 1 - immunology</subject><subject>Caspase 1 - metabolism</subject><subject>Caspase-1</subject><subject>Inflammasomes</subject><subject>Inflammasomes - immunology</subject><subject>Inflammasomes - metabolism</subject><subject>Inflammation</subject><subject>Interleukin 18</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mitochondria</subject><subject>Mitochondria - immunology</subject><subject>Mitochondria - metabolism</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - immunology</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Reactive oxygen species</subject><subject>Secretion</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1LAzEQhoMotlbvniTgxcvqJNkmjbdS_ChULaJXl2w2227ZbOomC_bfm9LWg6cZhmdeZh6ELgncppDKu1Vlbde4-pYIIIKyI9QnwyEknAM_Rn0AShMiuOihM-9XAMCBpqeoR2VshKB99DXpQqiaBX4oFuYev1TB6aVrirZSNR57b2xeb7ArcVga_Dp7nzM8bcpaWau8swZPnF3X5gdPfZxXoVLBFFgFPG8rG2PP0Umpam8u9nWAPh8fPibPyeztaToZzxKdEh4SLXUhylKyVAquclLmSjOiUkaGVALkpc65lLlQQIyWIyNHnBuhh2BYwZRSbIBudrnr1n13xofMVl6bulaNcZ3PKNDoi3AQEb3-h65c1zbxui0lYURTSSMFO0q3zvvWlNk6fqTaTUYg27rPDu6zvfu4crUP7nJrir-Fg2z2C6RkgOs</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Elliott, Eric I</creator><creator>Miller, Alexis N</creator><creator>Banoth, Balaji</creator><creator>Iyer, Shankar S</creator><creator>Stotland, Aleksandr</creator><creator>Weiss, Jerrold P</creator><creator>Gottlieb, Roberta A</creator><creator>Sutterwala, Fayyaz S</creator><creator>Cassel, Suzanne L</creator><general>American Association of Immunologists</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1476-4485</orcidid><orcidid>https://orcid.org/0000-0003-4794-1097</orcidid><orcidid>https://orcid.org/0000-0002-1432-006X</orcidid><orcidid>https://orcid.org/0000-0002-7467-2198</orcidid><orcidid>https://orcid.org/0000-0003-0630-3478</orcidid><orcidid>https://orcid.org/0000-0002-5384-2274</orcidid></search><sort><creationdate>20180501</creationdate><title>Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming</title><author>Elliott, Eric I ; Miller, Alexis N ; Banoth, Balaji ; Iyer, Shankar S ; Stotland, Aleksandr ; Weiss, Jerrold P ; Gottlieb, Roberta A ; Sutterwala, Fayyaz S ; Cassel, Suzanne L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-c9cd7ff934976ab1fbac31a43152900bfcb699b7a01ec98e9866e7c50e3d3aaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Activation</topic><topic>Animals</topic><topic>Calcium</topic><topic>Cardiolipin</topic><topic>Cardiolipins - immunology</topic><topic>Cardiolipins - metabolism</topic><topic>Caspase</topic><topic>Caspase 1 - immunology</topic><topic>Caspase 1 - metabolism</topic><topic>Caspase-1</topic><topic>Inflammasomes</topic><topic>Inflammasomes - immunology</topic><topic>Inflammasomes - metabolism</topic><topic>Inflammation</topic><topic>Interleukin 18</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mitochondria</topic><topic>Mitochondria - immunology</topic><topic>Mitochondria - metabolism</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - immunology</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Reactive oxygen species</topic><topic>Secretion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elliott, Eric I</creatorcontrib><creatorcontrib>Miller, Alexis N</creatorcontrib><creatorcontrib>Banoth, Balaji</creatorcontrib><creatorcontrib>Iyer, Shankar S</creatorcontrib><creatorcontrib>Stotland, Aleksandr</creatorcontrib><creatorcontrib>Weiss, Jerrold P</creatorcontrib><creatorcontrib>Gottlieb, Roberta A</creatorcontrib><creatorcontrib>Sutterwala, Fayyaz S</creatorcontrib><creatorcontrib>Cassel, Suzanne L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elliott, Eric I</au><au>Miller, Alexis N</au><au>Banoth, Balaji</au><au>Iyer, Shankar S</au><au>Stotland, Aleksandr</au><au>Weiss, Jerrold P</au><au>Gottlieb, Roberta A</au><au>Sutterwala, Fayyaz S</au><au>Cassel, Suzanne L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>200</volume><issue>9</issue><spage>3047</spage><epage>3052</epage><pages>3047-3052</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The NLRP3 inflammasome is activated in response to microbial and danger signals, resulting in caspase-1-dependent secretion of the proinflammatory cytokines IL-1β and IL-18. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Activation Animals Calcium Cardiolipin Cardiolipins - immunology Cardiolipins - metabolism Caspase Caspase 1 - immunology Caspase 1 - metabolism Caspase-1 Inflammasomes Inflammasomes - immunology Inflammasomes - metabolism Inflammation Interleukin 18 Mice Mice, Inbred C57BL Mice, Knockout Mitochondria Mitochondria - immunology Mitochondria - metabolism NLR Family, Pyrin Domain-Containing 3 Protein - immunology NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Reactive oxygen species Secretion |
| title | Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming |
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