PMID- 35129770 OWN - NLM STAT- MEDLINE DCOM- 20220516 LR - 20220531 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 45 IP - 3 DP - 2022 Jun TI - Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells in Sepsis. PG - 1374-1387 LID - 10.1007/s10753-022-01628-x [doi] AB - Dendritic cells (DCs) are vital antigen-presenting cells (APCs) in the immune system, whose apoptosis is closely related to the development of sepsis. Mitophagy is one of the necessary forms of selective autophagy that removes damaged or dysfunctional mitochondria to regulate immunity and inflammation. However, its effect on the apoptosis of DC in sepsis remains unknown. Here, we showed that sepsis activated the apoptosis and mitophagy of DC, and mitophagy had an anti-apoptotic effect on sepsis-induced DC apoptosis. In this study, we used cecal ligation and puncture (CLP) to simulate the pathophysiological state of sepsis. Apoptosis and mitophagy of DC were significantly enhanced in CLP mice compared with controls, and in the Pink1-KO (Pink1-knockout) mice CLP model, the level of apoptosis in DC was further increased while the level of mitophagy was decreased. In addition, more severe mitochondrial dysfunction was exhibited in DC of Pink1-KO mice CLP model compared to wild-type (WT) mice. The results suggest that Pink1/Parkin-mediated mitophagy is activated during sepsis and has an anti-apoptotic effect on DC, which regulates immune functions. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhang, Yaolu AU - Zhang Y AUID- ORCID: 0000-0003-2955-1386 AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Chen, Longwang AU - Chen L AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Luo, Yinan AU - Luo Y AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Department of Critical Care Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China. FAU - Wang, Kang AU - Wang K AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Liu, Xinyong AU - Liu X AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Xiao, Zhong AU - Xiao Z AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zhao, Guangju AU - Zhao G AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yao, Yongming AU - Yao Y AD - Trauma Research Center, Fourth Medical of the Chinese PLA General Hospital, Beijing, China. c_ff@sina.com. FAU - Lu, Zhongqiu AU - Lu Z AD - Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. lzq_640815@163.com. AD - Key Laboratory of Emergency & Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. lzq_640815@163.com. LA - eng PT - Journal Article DEP - 20220207 PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.3.2.27 (parkin protein) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (PTEN-induced putative kinase) SB - IM MH - Animals MH - Apoptosis MH - Dendritic Cells MH - Disease Models, Animal MH - Mice MH - Mice, Knockout MH - *Mitophagy/physiology MH - Protein Kinases/*metabolism MH - *Sepsis MH - Ubiquitin-Protein Ligases/*metabolism OTO - NOTNLM OT - E3 ubiquitin ligases/Parkin OT - PTEN-induced putative kinase 1/Pink1 OT - apoptosis OT - dendritic cell OT - mitophagy OT - sepsis. EDAT- 2022/02/08 06:00 MHDA- 2022/05/17 06:00 CRDT- 2022/02/07 12:15 PHST- 2021/03/09 00:00 [received] PHST- 2022/01/12 00:00 [accepted] PHST- 2021/12/23 00:00 [revised] PHST- 2022/02/08 06:00 [pubmed] PHST- 2022/05/17 06:00 [medline] PHST- 2022/02/07 12:15 [entrez] AID - 10.1007/s10753-022-01628-x [pii] AID - 10.1007/s10753-022-01628-x [doi] PST - ppublish SO - Inflammation. 2022 Jun;45(3):1374-1387. doi: 10.1007/s10753-022-01628-x. Epub 2022 Feb 7.