V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation

Oliver Florey, Noor Gammoh, Sung Eun Kim, Xuejun Jiang, Michael Overholtzer

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)


Recently a noncanonical activity of autophagy proteins has been discovered that targets lipidation of microtubule-associated protein 1 light chain 3 (LC3) onto macroendocytic vacuoles, including macropinosomes, phagosomes, and entotic vacuoles. While this pathway is distinct from canonical autophagy, the mechanism of how these nonautophagic membranes are targeted for LC3 lipidation remains unclear. Here we present evidence that this pathway requires activity of the vacuolar-type H+-ATPase (V-ATPase) and is induced by osmotic imbalances within endolysosomal compartments. LC3 lipidation by this mechanism is induced by treatment of cells with the lysosomotropic agent chloroquine, and through exposure to the Heliobacter pylori pore-forming toxin VacA. These data add novel mechanistic insights into the regulation of noncanonical LC3 lipidation and its associated processes, including LC3-associated phagocytosis (LAP), and demonstrate that the widely and therapeutically used drug chloroquine, which is conventionally used to inhibit autophagy flux, is an inducer of LC3 lipidation.

Original languageEnglish
Pages (from-to)88-99
Number of pages12
Issue number1
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a National Cancer Institute grant RO1CA154649, National Institutes of Health grants RO1CA166413 and 1F32CA162691, and by a Cancer Research UK fellowship C47718/A16337.

Publisher Copyright:
© 2015 Taylor & Francis Group, LLC.


  • Autophagy
  • Chloroquine
  • Entosis
  • Helicobacter pylori
  • LAP
  • LC3
  • Lysosome
  • Phagocytosis
  • V-ATPase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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