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Updated: Jul 24, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K

PTEN is both an activator and a substrate of chaperone-mediated autophagy

Katherine K Zhang1, Calvin M Burns2, Mary E Skinner3

  • 1College of Literature, Arts, and the Sciences, University of Michigan, Ann Arbor , Ann Arbor, MI, USA.

The Journal of Cell Biology
|July 7, 2023
PubMed

Insights

Overexpressing PTEN enhances chaperone-mediated autophagy (CMA), a process crucial for regulating metabolism and lifespan. This study reveals CMA as both an effector and regulator of PTEN, impacting cancer pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • PTEN (Phosphatase and tensin homolog) is a key tumor suppressor and negative regulator of the PI3K/AKT signaling pathway.
  • Mutations in PTEN are frequent in various cancers, highlighting its critical role in cell growth and survival.
  • PTEN overexpression in mice impacts metabolism, reduces fat, and extends lifespan.

Purpose of the Study:

  • To investigate the regulatory relationship between PTEN and chaperone-mediated autophagy (CMA).
  • To determine if PTEN influences CMA activity and vice versa.
  • To elucidate the role of CMA in mediating PTEN's metabolic and lifespan-extending effects.

Main Methods:

  • Utilized cultured cells and mouse models to study PTEN overexpression (OE) and knockdown.
  • Assessed CMA activity through various cellular and molecular assays.
  • Investigated the dependence of PTEN's effects on its lipid phosphatase activity and AKT signaling.
  • Analyzed metabolic shifts, including glycolysis and lipid droplet formation.
  • Examined PTEN protein stability and localization in lysosomes.

Main Results:

  • PTEN OE enhances CMA activity, dependent on PTEN's lipid phosphatase function and AKT inactivation.
  • PTEN knockdown reduces CMA, which is reversible by inhibiting PI3K or AKT.
  • Both PTEN and CMA negatively regulate glycolysis and lipid droplet formation.
  • Suppression of glycolysis and lipid droplet formation by PTEN OE is dependent on CMA.
  • PTEN protein levels are regulated by CMA, with PTEN accumulating in lysosomes when CMA is elevated.

Conclusions:

  • Chaperone-mediated autophagy (CMA) is demonstrated to be both an effector and a regulator of PTEN.
  • The interplay between PTEN and CMA influences key metabolic pathways and may contribute to PTEN's tumor-suppressive and lifespan-extending functions.
  • These findings reveal a novel regulatory axis with implications for cancer therapy and aging research.

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