Phosphorylated CAV1 activates autophagy through an interaction with BECN1 under oxidative stress

Cell Death Dis. 2017 May 25;8(5):e2822. doi: 10.1038/cddis.2017.71.


CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency. Under oxidative stress, CAV1 interacted with a complex of BECN1/VPS34 through its scaffolding domain, and this interaction facilitated autophagosome formation. Interestingly, the phosphorylation of CAV1 at tyrosine-14 was essential for the interaction with BECN1 and their localization to the mitochondria, and the activation of autophagy in response to hydrogen peroxide. In addition, the expression of a phosphatase PTPN1 reduced the phosphorylation of CAV1 and inhibited autophagy. Further, compared to that in wild-type mice, autophagy was impaired and cerebral infarct damage was aggravated in the brain of Cav1 knockout mice. These results suggest that the phosphorylated CAV1 functions to activate autophagy through binding to the BECN1/VPS34 complex under oxidative stress and to protect against ischemic damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Beclin-1 / metabolism*
  • Brain / pathology
  • Brain / ultrastructure
  • Brain Ischemia / pathology
  • Caveolin 1 / deficiency
  • Caveolin 1 / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / toxicity
  • Mice, Knockout
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Models, Biological
  • Oxidative Stress* / drug effects
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism


  • Beclin-1
  • Caveolin 1
  • Hydrogen Peroxide