Chaperone-Mediated Autophagy in Aging and Disease

Ashish C. Massey, Cong Zhang, Ana Maria Cuervo

Research output: Contribution to journalArticle

227 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)205-235
Number of pages31
JournalCurrent Topics in Developmental Biology
Volume73
DOIs
StatePublished - 2006

Fingerprint

Autophagy
Lysosomes
Lysosome-Associated Membrane Glycoproteins
Membranes
Molecular Chaperones
Proteolysis
Mammals
Cytoplasm
Proteins

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Chaperone-Mediated Autophagy in Aging and Disease. / Massey, Ashish C.; Zhang, Cong; Cuervo, Ana Maria.

In: Current Topics in Developmental Biology, Vol. 73, 2006, p. 205-235.

Research output: Contribution to journalArticle

@article{70f592406eff45e1b38bcc318ed230df,
title = "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.",
author = "Massey, {Ashish C.} and Cong Zhang and Cuervo, {Ana Maria}",
year = "2006",
doi = "10.1016/S0070-2153(05)73007-6",
language = "English (US)",
volume = "73",
pages = "205--235",
journal = "Current Topics in Developmental Biology",
issn = "0070-2153",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Chaperone-Mediated Autophagy in Aging and Disease

AU - Massey, Ashish C.

AU - Zhang, Cong

AU - Cuervo, Ana Maria

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33745023775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745023775&partnerID=8YFLogxK

U2 - 10.1016/S0070-2153(05)73007-6

DO - 10.1016/S0070-2153(05)73007-6

M3 - Article

C2 - 16782460

AN - SCOPUS:33745023775

VL - 73

SP - 205

EP - 235

JO - Current Topics in Developmental Biology

JF - Current Topics in Developmental Biology

SN - 0070-2153

ER -