Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy.
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 has 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 autophagy-related protein required for autophagosome formation, we have found that blockage of macroautophagy leads to up-regulation 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 it identifies changes in the lysosomal compartment that underlie the basis for the communication between both autophagic pathways.
Kaushik
Susmita
S
Departments of Anatomy and Structural Biology and Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Massey
Ashish C
AC
Mizushima
Noboru
N
Cuervo
Ana Maria
AM
D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002467:Cell Nucleus / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones