Mostrar el registro sencillo del ítem
dc.contributor.author
Moriwaki, Kenta
dc.contributor.author
Farias Luz, Nivea
dc.contributor.author
Balaji, Sakthi
dc.contributor.author
de Rosa, Maria Jose
dc.contributor.author
O'Donnell, Carey L.
dc.contributor.author
Gough, Peter J.
dc.contributor.author
Bertin, John
dc.contributor.author
Welsh, Raymond M.
dc.contributor.author
Chan, Francis Ka Ming
dc.date.available
2019-05-22T19:34:21Z
dc.date.issued
2016-01-18
dc.identifier.citation
Moriwaki, Kenta; Farias Luz, Nivea; Balaji, Sakthi; de Rosa, Maria Jose; O'Donnell, Carey L.; et al.; The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages; American Association of Immunologists; Journal of Immunology; 196; 1; 18-1-2016; 407-415
dc.identifier.issn
0022-1767
dc.identifier.uri
http://hdl.handle.net/11336/76893
dc.description.abstract
The cytokine IL-1β is intimately linked to many pathological inflammatory conditions. Mature IL-1β secretion requires cleavage by the inflammasome. Recent evidence indicates that many cell death signal adaptors have regulatory roles in inflammasome activity. These include the apoptosis inducers FADD and caspase 8, and the necroptosis kinases receptor interacting protein kinase 1 (RIPK1) and RIPK3. PGAM5 is a mitochondrial phosphatase that has been reported to function downstream of RIPK3 to promote necroptosis and IL-1β secretion. To interrogate the biological function of PGAM5, we generated Pgam5−/− mice. We found that Pgam5−/− mice were smaller compared with wild type littermates, and male Pgam5−/− mice were born at sub-Mendelian ratio. Despite these growth and survival defects, Pgam5−/− cells responded normally to multiple inducers of apoptosis and necroptosis. Rather, we found that PGAM5 is critical for IL-1β secretion in response to NLRP3 and AIM2 inflammasome agonists. Moreover, vesicular stomatosis virus–induced IL-1β secretion was impaired in Pgam5−/− bone marrow–derived macrophages, but not in Ripk3−/− bone marrow–derived dendritic cells, indicating that PGAM5 functions independent of RIPK3 to promote inflammasome activation. Mechanistically, PGAM5 promotes ASC polymerization, maintenance of mitochondrial integrity, and optimal reactive oxygen species production in response to inflammasome signals. Hence PGAM5 is a novel regulator of inflammasome and caspase 1 activity that functions independently of RIPK3.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association of Immunologists
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Necroptosis
dc.subject
Macrophages
dc.subject
Pgam5
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
The Mitochondrial Phosphatase PGAM5 Is Dispensable for Necroptosis but Promotes Inflammasome Activation in Macrophages
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-05-14T21:36:57Z
dc.identifier.eissn
1550-6606
dc.journal.volume
196
dc.journal.number
1
dc.journal.pagination
407-415
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Moriwaki, Kenta. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Farias Luz, Nivea. Universidade Federal da Bahia; Brasil. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Balaji, Sakthi. University of Massachussets; Estados Unidos
dc.description.fil
Fil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
dc.description.fil
Fil: O'Donnell, Carey L.. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Gough, Peter J.. Glaxo Smith Kline; Estados Unidos
dc.description.fil
Fil: Bertin, John. Glaxo Smith Kline; Estados Unidos
dc.description.fil
Fil: Welsh, Raymond M.. University of Massachussets; Estados Unidos
dc.description.fil
Fil: Chan, Francis Ka Ming. University of Massachussets; Estados Unidos
dc.journal.title
Journal of Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/196/1/407.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.4049/jimmunol.1501662
Archivos asociados