Chaperone-mediated autophagy in aging and disease
Abstract
Different mechanisms target intracellular components for their degradation into lysosomes through what is known as autophagy. In mammals, three main forms of autophagy have been described: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is the only autophagic pathway that allows selective degradation of soluble proteins in lysosomes. In contrast to the other mammalian forms of autophagy, CMA does not require vesicle formation or major changes in the lysosomal membrane. Instead, substrate proteins directly cross the lysosomal membrane to reach the lumen, where they are rapidly degraded. The substrate proteins are targeted to the lysosomal membrane by recognition of a targeting motif (a KFERQ-like motif), by a chaperone complex, consisting of hsc70 and its cochaperones, in the cytoplasm. Once at the lysosomal membrane, the protein interacts with a lysosomal receptor for this pathway, lysosomal associated membrane protein type 2A (LAMP-2A), and it is translocated across the membrane into the lysosomal lumen assisted by a lysosome resident chaperone. These two characteristics--selectivity and direct substrate translocation--determine the particular role of CMA in different physiological and pathological conditions. In this chapter, we cover current findings on the molecular mechanisms for CMA and the possible pathophysiological relevance of this selective lysosomal degradation.
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The number of autophagic vacuoles is significantly increased in the motor neurons of the spinal cords of SOD1G93A mice compared with controls.
“For example, the number of autophagic vacuoles is significantly increased in the motor neurons of the spinal cords of SOD1G93A mice compared with controls (Massey et al., 2006).”
From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Massey et al., 2006
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“For example, the number of autophagic vacuoles is significantly increased in the motor neurons of the spinal cords of SOD1G93A mice compared with controls (Massey et al., 2006).”
Background
- Authors
- Massey, A. C., Zhang, C., & Cuervo, A. M.
- Affiliations
- Albert Einstein College of Medicine (US)
- ORCID
- Zhang, Cong
- Venue
- Current Topics in Developmental Biology
- Publisher
- Elsevier
- Published
- 2006
- Volume
- 73
- Pages
- 205-235
- ISSN
- 0070-2153 (ISSN-L)
- OpenAlex
- W1487064198
- Cited by
- 315
- References
- 8
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 6 · 2023: 11 · 2022: 12 · 2021: 5 · 2020: 8 · 2019: 10 · 2018: 13 · 2017: 12 · 2016: 19 · 2015: 18 · 2014: 20 · 2013: 17 · 2012: 20
- FWCI
- 96.44
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Current topics in developmental biology/Current Topics in Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Institute on Aging (R03AG019834, AG19834, AG-021904, T32AG023475)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- chaperone-mediated autophagy, lysosomal degradation, selective protein degradation, Hsc70, LAMP2A, aging, disease, autophagy
- MeSH terms
- Aging, Animals, Autophagy, Disease, Humans, Kidney Diseases, Lysosomes, Oxidation-Reduction, Starvation, Lysosomal Storage Diseases, Antigen Presentation, Molecular Chaperones, Neurodegenerative Diseases
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