PMID- 33182075 OWN - NLM STAT- MEDLINE DCOM- 20210527 LR - 20210527 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 88 DP - 2020 Nov TI - FUN14 domain-containing 1-mediated mitophagy suppresses interleukin-1beta production in macrophages. PG - 106964 LID - S1567-5769(20)31388-6 [pii] LID - 10.1016/j.intimp.2020.106964 [doi] AB - Mitochondria play a critical role in triggering immune response. Although recent evidence indicates that autophagy/mitophagy can suppress inflammation via regulation of mitochondrial homeostasis, limited information is available regarding physiological regulation of mitochondria-controlled inflammation. In this study, we investigated FUN14 domain containing 1 (FUNDC1)-mediated mitophagy in the regulation of interleukin-1beta (IL-1beta) in vitro and in vivo, wild-type FUNDC1 and its mitophagy defective Y18A/L21A mutant were analyzed in bone marrow-derived macrophages (BMDMs)for their effects on IL-1beta expression and mitochondrial damage. The current study identified that LPS plus nigericin stimulation induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which was detected by IL-1beta expression. Moreover, FUNDC1-mediated mitophagy promoted the alleviation of intracellular reactive oxygen species (ROS). IL-1beta production was suppressed by the overexpression of wild-type FUNDC1, but not the Y18A/L21A mutant. Our results suggest that FUNDC1 suppresses LPS plus nigericin-mediated IL-1beta production through its regulatory effect on mitophagy, which will greatly promote the understanding of mitophagy-related protein in the regulation of immune response. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Huang, Jia AU - Huang J AD - Department of Intensive Care Unit, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China. FAU - Zhu, Tengfei AU - Zhu T AD - Department of Intensive Care Unit, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen 518112, China. FAU - Rong, Rong AU - Rong R AD - Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China. FAU - You, Mengling AU - You M AD - Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China. FAU - Ji, Dan AU - Ji D AD - Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Ophthalmogy, Central South University, Changsha 410008, Hunan Province, China. Electronic address: 475393400@qq.com. FAU - Li, Haibo AU - Li H AD - Eye Center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; Hunan Key Laboratory of Ophthalmogy, Central South University, Changsha 410008, Hunan Province, China. Electronic address: lihaibo151@aliyun.com. LA - eng PT - Journal Article DEP - 20200917 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (FUNDC1 protein, mouse) RN - 0 (IL1B protein, mouse) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - RRU6GY95IS (Nigericin) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Cells, Cultured MH - Inflammasomes/metabolism MH - Interleukin-1beta/*metabolism MH - Lipopolysaccharides MH - Macrophages/metabolism MH - Male MH - Membrane Proteins/*metabolism MH - Mice, Inbred C57BL MH - Mitochondrial Proteins/*metabolism MH - *Mitophagy MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Nigericin/pharmacology MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - FUNDC1 OT - IL-1beta OT - Macrophage OT - Mitophagy COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/11/14 06:00 MHDA- 2021/05/28 06:00 CRDT- 2020/11/13 01:01 PHST- 2020/05/02 00:00 [received] PHST- 2020/08/14 00:00 [revised] PHST- 2020/08/28 00:00 [accepted] PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/05/28 06:00 [medline] PHST- 2020/11/13 01:01 [entrez] AID - S1567-5769(20)31388-6 [pii] AID - 10.1016/j.intimp.2020.106964 [doi] PST - ppublish SO - Int Immunopharmacol. 2020 Nov;88:106964. doi: 10.1016/j.intimp.2020.106964. Epub 2020 Sep 17.