Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy

Ying Gao, Yajun Liu, Liang Hong, Zuolong Yang, Xinran Cai, Xiaoyun Chen, Yuanyuan Fu, Yujie Lin, Weijie Wen, Sitong Li, Xingguo Liu, Heqing Huang, Andreas Vogt, Peiqing Liu, Xiao Ming Yin, Min Li

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8 Scopus citations


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.

Original languageEnglish (US)
Article numbere2330
JournalCell Death and Disease
Issue number8
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Gao, Y., Liu, Y., Hong, L., Yang, Z., Cai, X., Chen, X., Fu, Y., Lin, Y., Wen, W., Li, S., Liu, X., Huang, H., Vogt, A., Liu, P., Yin, X. M., & Li, M. (2016). Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy. Cell Death and Disease, 7(8), [e2330]. https://doi.org/10.1038/cddis.2016.236