Chaperone-Mediated Autophagy and Aging: A Novel Regulatory Role of Lipids Revealed

Susmita Kaushik, Roberta Kiffin and Ana Maria Cuervo

volume 3 | issue 4

July/August 2007
Pages: 387 - 389

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

A wide pool of cytosolic proteins is selectively degraded in lysosomes by chaperone-mediated autophagy (CMA). Binding of these proteins to a receptor at the lysosomal membrane is the limiting step in CMA. Levels of this receptor are tightly regulated through changes in its degradation, multimeric organization and dynamic distribution between the lysosomal membrane and lumen. We have now reported that subcompartmentalization of the receptor in discrete lipid microdomains at the lysosomal membrane regulates its engagement in each of these processes — degradation, multimerization and membrane retrieval. Changes in the lipid composition of the membrane thus affect the dynamics of the receptor and, consequently, CMA activity. As an example of CMA dysfunction resulting from perturbation of the lipid composition of the lysosomal membrane, we discuss here a second study in which we analyzed the changes in the dynamics of the receptor during aging. CMA activity decreases with age primarily due to a decrease in the levels of the CMA receptor at the lysosomal membrane. Now we have found that age-related alterations in the lipid composition of the discrete microdomains at the lysosomal membrane are behind the reduced lysosomal levels of the receptor and, consequently, the declined CMA activity that occurs during aging.

Addendum to:
Altered Dynamics of the Lysosomal Receptor for Chaperone-Mediated Autophagy with Age
R. Kiffin, S. Kaushik, M. Zeng, U. Bandyopadhyay, C. Zhang, A.C. Massey, M. Martinez-Vicente and A.M. Cuervo
J Cell Sci 2007; 120:782-91
and
Lysosome Membrane Lipid Microdomains: Novel Regulators of Chaperone-Mediated Autophagy
S. Kaushik, A.C. Massey and A.M. Cuervo
EMBO J 2006; 25:3921-33

Authors

Susmita Kaushik

Albert Einstein College of Medicine

Roberta Kiffin

Albert Einstein College of Medicine

Ana Maria Cuervo

Department of Development and Molecular Biology; Marion Bessin Liver Research Center; Institute for Aging Studies; Albert Einstein College of Medicine; Bronx, New York USA

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: