title: Phosphorylation of dynamin-related protein 1 at Ser616 regulates mitochondrial fission and is involved in mitochondrial calcium uniporter-mediated neutrophil polarization and chemotaxis.
abstract: During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca2+uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes. We also provide evidence that this role of the MCU in neutrophils may result from modulation of mitochondrial fission by increased levels of pDrp1 S616 via accumulation of Ca2+into the mitochondrial matrix. Thus, our study identifies the dependence of neutrophil polarization and chemotaxis on the MCU and highlights the importance of regulating mitochondrial fission during the anti-inflammatory cascade in human neutrophils.
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Xianchong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Chu
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address: h_zcn@126.com.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address: zoufei616@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D002633:Chemotaxis / Q000502:physiology*; D034281:Dynamins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015220:Calcium Channels; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C034703:mitochondrial calcium uniporter; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins; D002118:Calcium
keywords: Dynamin-related protein 1 (Drp1); Inflammation; Mitochondrial calcium uniporter (MCU); Mitochondrial fission; Neutrophil polarization