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Browsing by Author "Zheng, Zhihua"
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Item Niclosamide Triggers Non-Canonical LC3 Lipidation(MDPI, 2019-03-15) Liu, Yajun; Luo, Xia; Shan, Hao; Fu, Yuanyuan; Gu, Qianqian; Zheng, Xueping; Dai, Qi; Xia, Fan; Zheng, Zhihua; Liu, Peiqing; Yin, Xiao-Ming; Hong, Liang; Li, Min; Pathology and Laboratory Medicine, School of MedicineAutophagy 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.