Browsing by Author "Liu, Yajun"

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    Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy
    (Nature Publishing Group, 2016-08-11) Gao, Ying; Liu, Yajun; Hong, Liang; Yang, Zuolong; Cai, Xinran; Chen, Xiaoyun; Fu, Yuanyuan; Lin, Yujie; Wen, Weijie; Li, Sitong; Liu, Xingguo; Huang, Heqing; Vogt, Andreas; Liu, Peiqing; Yin, Xiao-Ming; Li, Min; Department of Pathology and Laboratory Medicine, School of Medicine
    Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1) complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase) inhibitors, but not by disturbance of the lysosome function or the intracellular ion redistribution. Similar findings were applicable to a diverse group of stimuli that can induce noncanonical autophagy in a FIP200-independent manner. AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex was also required for multiple other agents to stimulate noncanonical LC3 lipidation. These results suggest that the Golgi complex may serve as a membrane platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase inhibitors could be useful tools for studying noncanonical autophagy.
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    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 Medicine
    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.