P53 regulates Chaperone-mediated autophagy

ABSTRACT:

p53 protects against the initiation and progression of a plethora of cancers, but the mechanisms underlying this critical function remain incompletely understood. In addition, chaperone-mediated autophagy (CMA) is major form of autophagy unique to vertebrates, yet both its regulation and function are unclear. Here, we demonstrate that p53 acts as a central activator of CMA, integrating diverse stress signals to regulate this highly selective autophagic pathway. Mechanistically, AMPK—a key cellular energy sensor—inhibits CMA by abrogating the oligomerization of the CMA receptor LAMP2A. Cytoplasmic p53 interacts with AMPK and relieves its inhibitory effect. By activating CMA, p53 targets isocitrate dehydrogenases IDH1 and IDH2 for degradation, inhibiting reductive conversion of glutamine to citrate and suppressing oncogenic growth. Tumor-associated p53 mutants lack the CMA-promoting activities, while oncogenic IDH mutants are resistant to p53- and CMA-mediated degradation. These results suggest that activation of CMA may be a fundamental component of p53 biological function, through which it modulates metabolism and inhibits oncogenic growth. 

INSTRUMENT(S): Liquid Chromatography MS -

PROVIDER: MTBLS13190 | MetaboLights | 2026-10-03

REPOSITORIES: MetaboLights