Niclosamide Triggers Non-Canonical LC3 Lipidation

Cells

Xiao-Ming Yin¹  Xia Luo²  Qianqian Gu²  Xueping Zheng²  Liang Hong²  Yajun Liu²  Zhihua Zheng²  Qi Dai²  Hao Shan²  Min Li²  Yuanyuan Fu²  Fan Xia²  Peiqing Liu² 

[1] Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA;School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China;

关键词: autophagy;    bafilomycin A1;    Golgi complex;    niclosamide;    non-canonical LC3 lipidation;    vimentin;   

DOI  :  10.3390/cells8030248

来源: DOAJ

【 摘 要 】

Autophagy 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.

【 授权许可】

Unknown