PMID- 35686354 OWN - NLM STAT- MEDLINE DCOM- 20220919 LR - 20220919 IS - 1099-0461 (Electronic) IS - 1095-6670 (Linking) VI - 36 IP - 9 DP - 2022 Sep TI - Mitoquinone mitigates paraquat-induced A549 lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion. PG - e23127 LID - 10.1002/jbt.23127 [doi] AB - Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury. CI - (c) 2022 Wiley Periodicals LLC. FAU - Liu, Chao AU - Liu C AUID- ORCID: 0000-0002-0315-2195 AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Sun, Zhaorui AU - Sun Z AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Wang, Mengmeng AU - Wang M AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Yang, Zhizhou AU - Yang Z AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Zhang, Wei AU - Zhang W AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Ren, Yi AU - Ren Y AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Han, Xiaoqin AU - Han X AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Zhang, Bo AU - Zhang B AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Yao, Mengya AU - Yao M AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. FAU - Nie, Shinan AU - Nie S AD - Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. LA - eng GR - 2020M683718/China Postdoctoral Science Foundation/ GR - BK20190247/National Natural Science Foundation of Jiangsu Province/ GR - BK20211136/National Natural Science Foundation of Jiangsu Province/ GR - 82102311/National Natural Science Foundation of China/ GR - 82172182/National Natural Science Foundation of China/ PT - Journal Article DEP - 20220609 PL - United States TA - J Biochem Mol Toxicol JT - Journal of biochemical and molecular toxicology JID - 9717231 RN - 0 (Antioxidants) RN - 0 (Mitochondrial Membrane Transport Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Organophosphorus Compounds) RN - 0 (Reactive Oxygen Species) RN - 1339-63-5 (Ubiquinone) RN - 47BYS17IY0 (mitoquinone) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (MFN2 protein, human) RN - EC 3.6.5.- (Mfn1 protein, human) RN - PLG39H7695 (Paraquat) SB - IM MH - A549 Cells MH - Antioxidants/pharmacology MH - GTP Phosphohydrolases/pharmacology MH - Humans MH - Lung/metabolism MH - *Lung Injury MH - Mitochondrial Dynamics MH - Mitochondrial Membrane Transport Proteins MH - Mitochondrial Proteins MH - Organophosphorus Compounds MH - *Paraquat/toxicity MH - Reactive Oxygen Species/metabolism MH - Ubiquinone/analogs & derivatives OTO - NOTNLM OT - A549 cells OT - lung injury OT - mitochondrial fusion OT - mitoquinone OT - paraquat EDAT- 2022/06/11 06:00 MHDA- 2022/09/20 06:00 CRDT- 2022/06/10 03:03 PHST- 2022/04/16 00:00 [revised] PHST- 2021/10/11 00:00 [received] PHST- 2022/05/29 00:00 [accepted] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/09/20 06:00 [medline] PHST- 2022/06/10 03:03 [entrez] AID - 10.1002/jbt.23127 [doi] PST - ppublish SO - J Biochem Mol Toxicol. 2022 Sep;36(9):e23127. doi: 10.1002/jbt.23127. Epub 2022 Jun 9.