V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation Journal Article

   


Authors: Florey, O.; Gammoh, N.; Kim, S. E.; Jiang, X.; Overholtzer, M.
Article Title: V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation
Abstract: 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. © 2015 Taylor & Francis Group, LLC.
Keywords: unclassified drug; human cell; nonhuman; animal cell; mouse; cell compartmentalization; light chain; enzyme activity; autophagy; phagocytosis; helicobacter pylori; lysosome; chloroquine; endosome; cell vacuole; degradation; lc3; entosis; microtubule associated protein 1; microtubule associated protein 1 light chain 3; human; article; osmosis; lap; v-atpase; monensin; proton transporting adenosine triphosphatase; vacuolar type proton transporting adenosine triphosphatase; vacuolating toxin
Journal Title: Autophagy
Volume: 11
Issue: 1
ISSN: 1554-8627
Publisher: Taylor & Francis Group  
Date Published: 2015-01-01
Start Page: 88
End Page: 99
Language: English
DOI: 10.4161/15548627.2014.984277
PROVIDER: scopus
PUBMED: 25484071
PMCID: PMC4502810
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84923341785&partnerID=40&md5=738a099a507673dd3b14a5bbcf0c5345
Notes: Export Date: 2 April 2015 -- Source: Scopus
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MSK Authors
  1. Michael H Overholtzer
    81 Overholtzer
  2. Noor I Gammoh
    8 Gammoh
  3. Oliver Florey
    10 Florey
  4. Xuejun Jiang
    122 Jiang
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