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MBC in Press, published online ahead of print March 12, 2008
Mol. Biol. Cell 10.1091/mbc.E07-11-1155

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Submitted on November 19, 2007
Revised on February 20, 2008
Accepted on March 3, 2008

Constitutive Activation of Chaperone-mediated Autophagy in Cells with Impaired Macroautophagy

Susmita Kaushik,* Ashish C. Massey,* Noboru Mizushima,{dagger} and Ana Maria Cuervo*

*Department of Anatomy and Structural Biology, Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461; {dagger}Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan

Monitoring Editor: Suresh Subramani

Three different types of autophagy - macroautophagy, microautophagy and chaperone-mediated autophagy (CMA) - contribute to degradation of intracellular components in lysosomes in mammalian cells. Although some level of basal macroautophagy and CMA activities have been described in different cell types and tissues, these two pathways are maximally activated under stress conditions. Activation of these two pathways is often sequential, suggesting the existence of some level of cross-talk between both stress-related autophagic pathways. In this work we analyze the consequences of blockage of macroautophagy on CMA activity. Using mouse embryonic fibroblasts deficient in Atg5, an autophagic-related protein required for autophagosome formation, we have found that blockage of macroautophagy leads to upregulation of CMA, even under basal conditions. Interestingly, different mechanisms contribute to the observed changes in CMA-related proteins and the consequent activation of CMA during basal and stress conditions in these macroautophagy-deficient cells. This work supports a direct cross-talk between these two forms of autophagy and identifies changes in the lysosomal compartment that underlie the basis for the communication between both autophagic pathways.

Address correspondence to: Ana Maria Cuervo (amcuervo{at}aecom.yu.edu)






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