Liu, YajunLuo, XiaShan, HaoFu, YuanyuanGu, QianqianZheng, XuepingDai, QiXia, FanZheng, ZhihuaLiu, PeiqingYin, Xiao-MingHong, LiangLi, Min2019-08-092019-08-092019-03-15Liu, Y., Luo, X., Shan, H., Fu, Y., Gu, Q., Zheng, X., … Li, M. (2019). Niclosamide Triggers Non-Canonical LC3 Lipidation. Cells, 8(3), 248. doi:10.3390/cells8030248https://hdl.handle.net/1805/20278Autophagy is a highly- evolutionarily-conserved catabolic pathway activated by various cellular stresses. Recently, non-canonical autophagy (NCA), which does not require all of the ATG proteins to form autophagosome or autophagosome-like structures, has been found in various conditions. Moreover, mounting evidence has indicated that non-canonical LC3 lipidation (NCLL) may reflect NCA. We and others have reported that niclosamide (Nic), an anti-helminthic drug approved by the Food and Drug Administration, could induce canonical autophagy via a feedback downregulation of mTOR complex 1. In this study, we found that Nic could also induce NCLL, which is independent of the ULK1 complex and Beclin 1 complex, but dependent on ubiquitin-like conjugation systems. Although bafilomycin A1 and concanamycin A, two known V-ATPase inhibitors, significantly inhibited Nic-induced NCLL, Nic-induced NCLL was demonstrated to be independent of V-ATPase. In addition, the Golgi complex and vimentin were involved in Nic-induced NCLL, which might be a platform or membrane source for Nic-induced LC3-positive structures. These results would be helpful to broaden our understanding of the working mechanisms of Nic and evaluate its pharmacological activities in diseases.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesGolgi complexAutophagyBafilomycin A1NiclosamideNon-canonical LC3 lipidationVimentinArticle