title: Modulation of autophagic activity by extracellular pH.
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.
authors: Department of Radiation Oncology, Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Teng
authors: T
authors: Xu
authors: Hang
authors: H
authors: Su
authors: Suthakar
authors: S
authors: Ganapathy
authors: Zhi-Min
authors: ZM
authors: Yuan
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins