Modulation of autophagic activity by extracellular pH

Teng Xu, Hang Su, Suthakar Ganapathy, Zhi Min Yuan

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Reprogramming energy metabolism from oxidative phosphorylation to aerobic glycolysis, a common feature of human cancer, is associated with a relative acidic tumor microenvironment which can sometimes be further accentuated by hypoxia operating within most solid tumors. We found that alteration of extracellular pH induces marked and rapid changes of autophagic activity. Interestingly, acidic and basic conditions induced completely opposite effect on autophagy, with its activity suppressed at lower pH whereas stimulated at higher pH. Gene knockdown experiments indicated that pH induced-autophagy requires Beclin 1, Vps34 and Atg5, key components of the autophagy pathway. Of note, an acidic condition not only inhibits the basal but also blocks the starvation-induced autophagy activity. Significantly, examination of different areas of tumor mass revealed a lower autophagic activity within the inner region than the outer region. These findings have important implications on the connections between autophagy and cancer as well as a wide range of other physiological and pathological processes.

Original languageEnglish (US)
Pages (from-to)1316-1322
Number of pages7
JournalAutophagy
Volume7
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Atg5
  • Autophagy
  • Beclin 1
  • Cancer
  • Extracellular pH
  • Microenvironment
  • VPS34

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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