Cited by 213Autophagy in Disease and TherapyGenetics, Aging, and Longevity in Model OrganismsCellular transport and secretion

Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age

Kiffin, Roberta, Kaushik, Susmita, Zeng, Mei, Bandyopadhyay, Urmi, Zhang, Cong, Massey, Ashish C., Martinez-Vicente, Marta, Cuervo, Ana Maria·2007·Journal of Cell Science

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.

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Crossref · 10.1242/jcs.001073

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  • Changes with age in the lipid composition of the lysosomal membrane are likely behind the instability of LAMP-2A in old organisms.

    “Changes with age in the lipid composition of the lysosomal membrane are likely behind the instability of LAMP-2A in old organisms (Kiffin et al., 2007).”

    From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Kiffin et al., 2007

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Authors
Kiffin, R., Kaushik, S., Zeng, M., Bandyopadhyay, U., Zhang, C., Massey, A. C., Martinez-Vicente, M., & Cuervo, A. M.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Department of Anatomy and Structural Biology, Department of Developmental and Molecular Biology and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Venue
Journal of Cell Science
Published
2007-03-01
Volume
120
Issue
5
Pages
782-791
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
OpenAlex
W1990012982
Cited by
213
References
36
Citations by year
2026: 5 · 2025: 8 · 2024: 15 · 2023: 13 · 2022: 12 · 2021: 13 · 2020: 9 · 2019: 12 · 2018: 16 · 2017: 10 · 2016: 11 · 2015: 12 · 2014: 7 · 2013: 10 · 2012: 8
FWCI
9.21
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01AG021904, AG-25355, AG-NS-0163, AG-021904, R21AG025355, T32AG023475)
  • National Institute of General Medical Sciences (T32GM007491)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
chaperone-mediated autophagy, LAMP2A, aging, lysosomal membrane, receptor turnover, proteolytic cleavage, lipid rafts, lysosomal clearance
MeSH terms
Aging, Animals, Autophagy, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Lysosomes, Male, Peptide Hydrolases, Rats, Inbred F344, RNA, Messenger, Immunoblotting, Gene Expression, Molecular Chaperones, Reverse Transcriptase Polymerase Chain Reaction, Membrane Microdomains, Rats, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 2

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