Consequences of the selective blockage of chaperone-mediated autophagy

Ashish C. Massey, Susmita Kaushik, Guy Sovak, Roberta Kiffin, Ana Maria Cuervo

Research output: Contribution to journalArticlepeer-review

350 Scopus citations

Abstract

Chaperone-mediated autophagy (CMA) is a selective pathway for the degradation of cytosolic proteins in lysosomes. CMA declines with age because of a decrease in the levels of lysosome-associated membrane protein (LAMP) type 2A, a lysosomal receptor for this pathway. We have selectively blocked the expression of LAMP-2 A in mouse fibroblasts in culture and analyzed the cellular consequences of reduced CMA activity. CMA-defective cells maintain normal rates of long-lived protein degradation by up-regulating macroautophagy, the major form of autophagy. Constitutive upregulation of macroautophagy is unable, however, to compensate for all CMA functions. Thus, CMA-defective cells are more sensitive to Stressors, suggesting that, although protein turnover is maintained, the selectivity of CMA is necessary as part of the cellular response to stress. Our results also denote the existence of cross-talk among different forms of autophagy.

Original languageEnglish (US)
Pages (from-to)5805-5810
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number15
DOIs
StatePublished - Apr 11 2006

Keywords

  • Lysosome membrane proteins
  • Lysosomes
  • Macroautophagy
  • Proteases
  • Protein degradation

ASJC Scopus subject areas

  • General

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