Chaperone-mediated Autophagy in Protein Quality Control

Overview

Journal Curr Opin Cell Biol

Publisher Elsevier

Specialty Cell Biology

Date 2010 Nov 25

PMID 21094035

Citations 152

Authors

Esperanza Arias

Ana Maria Cuervo

Affiliations

Soon will be listed here.

Abstract

Chaperone-mediated autophagy is a selective mechanism for degradation of soluble cytosolic proteins in lysosomes that distinguishes itself from other autophagic pathways by the selectivity with which CMA substrates are targeted for degradation. The recent molecular dissection of this autophagic pathway and the development of experimental models with compromised CMA have unveiled the important contribution of this pathway to protein quality control. In fact, CMA activation seems to be a common mechanism of cellular defense against proteotoxicity.

Citing Articles

Molecular mechanisms of autophagy and implications in liver diseases.

Wu Y, Tan H, Lin J, Shen H, Wang H, Lu G Liver Res. 2025; 7(1):56-70.

PMID: 39959698 PMC: 11792062. DOI: 10.1016/j.livres.2023.02.002.

Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.

Wu J, Xu W, Su Y, Wang G, Ma J Acta Pharmacol Sin. 2024; .

PMID: 39548290 DOI: 10.1038/s41401-024-01416-3.

Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).

Huang J, Wang J Mol Med Rep. 2024; 31(1).

PMID: 39513615 PMC: 11542157. DOI: 10.3892/mmr.2024.13378.

Proteostasis and Its Role in Disease Development.

Shukla M, Narayan M Cell Biochem Biophys. 2024; .

PMID: 39422790 DOI: 10.1007/s12013-024-01581-6.

TDRD3 functions as a selective autophagy receptor with dual roles in autophagy and modulation of stress granule stability.

Deater M, Lloyd R bioRxiv. 2024; .

PMID: 39345463 PMC: 11430058. DOI: 10.1101/2024.09.22.614367.

References

Agarraberes F, Dice J . A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J Cell Sci. 2001; 114(Pt 13):2491-9. DOI: 10.1242/jcs.114.13.2491. View

Agarraberes F, Terlecky S, Dice J . An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol. 1997; 137(4):825-34. PMC: 2139836. DOI: 10.1083/jcb.137.4.825. View

Cuervo A, Knecht E, Terlecky S, Dice J . Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am J Physiol. 1995; 269(5 Pt 1):C1200-8. DOI: 10.1152/ajpcell.1995.269.5.C1200. View

Cuervo A, Gomes A, Barnes J, Dice J . Selective degradation of annexins by chaperone-mediated autophagy. J Biol Chem. 2000; 275(43):33329-35. DOI: 10.1074/jbc.M005655200. View

Dice J . Chaperone-mediated autophagy. Autophagy. 2007; 3(4):295-9. DOI: 10.4161/auto.4144. View

Cuervo A, Hu W, Lim B, Dice J . IkappaB is a substrate for a selective pathway of lysosomal proteolysis. Mol Biol Cell. 1998; 9(8):1995-2010. PMC: 25451. DOI: 10.1091/mbc.9.8.1995. View

Yang Q, She H, Gearing M, Colla E, Lee M, Shacka J . Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science. 2009; 323(5910):124-7. PMC: 2666000. DOI: 10.1126/science.1166088. View

Sooparb S, Price S, Shaoguang J, Franch H . Suppression of chaperone-mediated autophagy in the renal cortex during acute diabetes mellitus. Kidney Int. 2004; 65(6):2135-44. DOI: 10.1111/j.1523-1755.2004.00639.x. View

Cuervo A, Dice J . Age-related decline in chaperone-mediated autophagy. J Biol Chem. 2000; 275(40):31505-13. DOI: 10.1074/jbc.M002102200. View

10.

Wang Y, Martinez-Vicente M, Kruger U, Kaushik S, Wong E, Mandelkow E . Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. Hum Mol Genet. 2009; 18(21):4153-70. PMC: 2758146. DOI: 10.1093/hmg/ddp367. View

11.

Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L . Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem. 2008; 283(35):23542-56. PMC: 2527094. DOI: 10.1074/jbc.M801992200. View

12.

Kaushik S, Massey A, Cuervo A . Lysosome membrane lipid microdomains: novel regulators of chaperone-mediated autophagy. EMBO J. 2006; 25(17):3921-33. PMC: 1560360. DOI: 10.1038/sj.emboj.7601283. View

13.

Cuervo A, Stefanis L, Fredenburg R, Lansbury P, Sulzer D . Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 2004; 305(5688):1292-5. DOI: 10.1126/science.1101738. View

14.

Morimoto R, Cuervo A . Protein homeostasis and aging: taking care of proteins from the cradle to the grave. J Gerontol A Biol Sci Med Sci. 2009; 64(2):167-70. PMC: 2655025. DOI: 10.1093/gerona/gln071. View

15.

Ciechanover A . Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol. 2005; 6(1):79-87. DOI: 10.1038/nrm1552. View

16.

Kon M, Cuervo A . Chaperone-mediated autophagy in health and disease. FEBS Lett. 2009; 584(7):1399-404. PMC: 2843772. DOI: 10.1016/j.febslet.2009.12.025. View

17.

Cuervo A, Dice J . Regulation of lamp2a levels in the lysosomal membrane. Traffic. 2001; 1(7):570-83. DOI: 10.1034/j.1600-0854.2000.010707.x. View

18.

Bauer P, Goswami A, Wong H, Okuno M, Kurosawa M, Yamada M . Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat Biotechnol. 2010; 28(3):256-63. DOI: 10.1038/nbt.1608. View

19.

Cuervo A, Hildebrand H, Bomhard E, Dice J . Direct lysosomal uptake of alpha 2-microglobulin contributes to chemically induced nephropathy. Kidney Int. 1999; 55(2):529-45. DOI: 10.1046/j.1523-1755.1999.00268.x. View

20.

Kiffin R, Christian C, Knecht E, Cuervo A . Activation of chaperone-mediated autophagy during oxidative stress. Mol Biol Cell. 2004; 15(11):4829-40. PMC: 524731. DOI: 10.1091/mbc.e04-06-0477. View