气候变化领域集成服务门户(CCPortal): Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation

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DOI	10.1073/PNAS.2015632118
	Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation
	Dagvadorj J.; Mikulska-Ruminska K.; Tumurkhuu G.; Ratsimandresy R.A.; Carriere J.; Andres A.M.; Marek-Iannucci S.; Song Y.; Chen S.; Lane M.; Dorfleutner A.; Gottlieb R.A.; Stehlik C.; Cassel S.; Sutterwala F.S.; Bahar I.; Crother T.R.; Arditi M.
发表日期	2021
ISSN	00278424
卷号	118 期号:1
英文摘要	The balance between NLRP3 inflammasome activation and mitophagy is essential for homeostasis and cellular health, but this relationship remains poorly understood. Here we found that interleukin-1α (IL-1α)–deficient macrophages have reduced caspase-1 activity and diminished IL-1β release, concurrent with reduced mitochondrial damage, suggesting a role for IL-1α in regulating this balance. LPS priming of macrophages induced pro-IL-1α translocation to mitochondria, where it directly interacted with mitochondrial cardiolipin (CL). Computational modeling revealed a likely CL binding motif in pro-IL-1α, similar to that found in LC3b. Thus, binding of pro-IL-1α to CL in activated macrophages may interrupt CL-LC3b–dependent mitophagy, leading to enhanced Nlrp3 inflammasome activation and more robust IL-1β production. Mutation of pro-IL-1α residues predicted to be involved in CL binding resulted in reduced pro-IL-1α–CL interaction, a reduction in NLRP3 inflammasome activity, and increased mitophagy. These data identify a function for pro-IL-1α in regulating mitophagy and the potency of NLRP3 inflammasome activation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autophagy; Cardiolipin; IL-1α; Inflammasome; Mitochondria
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181131
作者单位	Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Institute of Physics, Faculty of Physics Astronomy and Informatics, Nicolaus Copernicus University in Torun, Torun, 87-100, Poland; Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States; Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 9...
推荐引用方式 GB/T 7714	Dagvadorj J.,Mikulska-Ruminska K.,Tumurkhuu G.,et al. Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation[J],2021,118(1).
APA	Dagvadorj J..,Mikulska-Ruminska K..,Tumurkhuu G..,Ratsimandresy R.A..,Carriere J..,...&Arditi M..(2021).Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA	Dagvadorj J.,et al."Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).