Details

Autor(en) / Beteiligte

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

Titel

Consequences of the Selective Blockage of Chaperone-Mediated Autophagy

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2006-04, Vol.103 (15), p.5805-5810

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-2A 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.