Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age - PubMed (original) (raw)
. 2007 Mar 1;120(Pt 5):782-91.
doi: 10.1242/jcs.001073. Epub 2007 Feb 6.
Affiliations
- PMID: 17284523
- DOI: 10.1242/jcs.001073
Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age
Roberta Kiffin et al. J Cell Sci. 2007.
Abstract
Rates of autophagy, the mechanism responsible for lysosomal clearance of cellular components, decrease with age. We have previously described an age-related decline in chaperone-mediated autophagy (CMA), a selective form of autophagy, by which particular cytosolic proteins are delivered to lysosomes after binding to the lysosome-associated membrane protein type 2A (LAMP-2A), a receptor for this pathway. Rates of CMA decrease with age because of a decrease in the levels of LAMP-2A. In this work we have investigated the reasons for the reduced levels of LAMP-2A with age. While transcriptional rates of LAMP-2A remain unchanged with age, the dynamics and stability of the receptor in the lysosomal compartment are altered. The mobilization of the lysosomal lumenal LAMP-2A to the membrane when CMA is activated is altered in lysosomes from old animals, leading to the presence of an unstable pool of lumenal LAMP-2A. By contrast, the regulated cleavage of LAMP-2A at the lysosomal membrane is reduced owing to altered association of the receptor and the protease responsible for its cleavage to particular membrane microdomain regions. We conclude that age-related changes at the lysosomal membrane are responsible for the altered turnover of the CMA receptor in old organisms and the consequent decline in this pathway.
Comment in
- Chaperone-mediated autophagy and aging: a novel regulatory role of lipids revealed.
Kaushik S, Kiffin R, Cuervo AM. Kaushik S, et al. Autophagy. 2007 Jul-Aug;3(4):387-9. doi: 10.4161/auto.4246. Epub 2007 Jul 9. Autophagy. 2007. PMID: 17438364
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