PTEN activates chaperone-mediated autophagy to regulate metabolism

ABSTRACT

PTEN is a negative modulator of the INS-PI3K-AKT pathway and is an essential regulator of metabolism and cell growth. PTEN is one of the most commonly mutated tumor suppressors in cancer. However, PTEN overexpression extends the lifespan of both sexes of mice. We recently showed that PTEN is necessary and sufficient to activate chaperone-mediated autophagy (CMA) in the mouse liver and cultured cells. Selective protein degradation via CMA is required to suppress glycolysis and fatty acid synthesis when PTEN is overexpressed. Thus, activation of CMA downstream of PTEN might modulate health and metabolism through selective degradation of key metabolic enzymes.

KEYWORDS:

• Aging
• autophagy
• chaperone-mediated autophagy
• metabolism
• PTEN

Disclosure statement

The authors have no financial conflicts of interest to disclose.

Additional information

Funding

This work was supported by U01-AG022303-18 and U19-AG023122-11 to RAM, by 5P30-AG024824 to Raymond Yung and with sub-awards to SJE, by the Hevolution Foundation grant HF-AGE005 to SJE.