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Chaperone-Mediated Autophagy

  • Qian YangEmail author
  • Ronglin Wang
  • Lin Zhu
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1206)

Abstract

Protein homeostasis is essential for maintaining cell survival. Protein synthesis and degradation coordinately regulate protein homeostasis. Chaperone-mediated autophagy (CMA) was the first lysosomal process to be discovered by which intracellular components are selectively degraded. This process involves the recognition of the substrate, the unfolding and translocation of the substrate, and the degradation of the substrate. By degrading specific target proteins in a timely manner, CMA is involved in a variety of cellular activities. In the past few years, we have acquired a better understanding of how CMA is regulated. It has been reported that peroxide accumulation, aging and/or other pathological signals interfere with CMA function, which in turn induces neurodegenerative diseases, cancer, and other diseases. Combining results from the current research, we summarize the basic processes, regulatory mechanisms, and physiological functions of CMA and discuss its critical role in the development of diseases.

Keywords

Chaperone-mediated autophagy (CMA) Basic process Regulation Physiological function Microautophagy 

References

  1. Agarraberes FA, Terlecky SR, Dice JF (1997) An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J Cell Biol 137(4):825–834CrossRefGoogle Scholar
  2. Alvarez-Erviti L, Rodriguez-Oroz MC, Cooper JM, Caballero C, Ferrer I, Obeso JA, Schapira AH (2010) Chaperone-mediated autophagy markers in Parkinson disease brains. Arch Neurol 67(12):1464–1472CrossRefGoogle Scholar
  3. Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246(4928):382–385CrossRefGoogle Scholar
  4. Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273(5274):501–503CrossRefGoogle Scholar
  5. Cuervo AM, Wong E (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24(1):92–104CrossRefGoogle Scholar
  6. Dice JF (1990) Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem Sci 15(8):305–309CrossRefGoogle Scholar
  7. Dubouloz F, Deloche O, Wanke V, Cameroni E, de Virgilio C (2005) The TOR and EGO protein complexes orchestrate microautophagy in yeast. Mol Cell 19(1):15–26CrossRefGoogle Scholar
  8. Finn PF, Dice JF (2005) Ketone bodies stimulate chaperone-mediated autophagy. J Biol Chem 280(27):25864–25870CrossRefGoogle Scholar
  9. Kaushik S, Cuervo AM (2018) The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 19(6):365–381CrossRefGoogle Scholar
  10. Kon M, Kiffin R, Koga H, Chapochnick J, Macian F, Varticovski L, Cuervo AM (2011) Chaperone-mediated autophagy is required for tumor growth. Sci Transl Med 3(109):109ra117CrossRefGoogle Scholar
  11. Li WW, Li J, Bao JK (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69(7):1125–1136CrossRefGoogle Scholar
  12. Li W, Nie T, Xu H, Yang J, Yang Q, Mao Z (2019) Chaperone-mediated autophagy: advances from bench to bedside. Neurobiol Dis 12241–48Google Scholar
  13. Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, Wang G, Huang Y, Xiong Y, Guan KL, Lei QY (2011) Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth. Mol Cell 42(6):719–730CrossRefGoogle Scholar
  14. Mijaljica D, Prescott M, Devenish RJ (2011) Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7(7):673–682CrossRefGoogle Scholar
  15. Mukherjee A, Patel B, Koga H, Cuervo AM, Jenny A (2016) Selective endosomal microautophagy is starvation-inducible in Drosophila. Autophagy 12(11):1984–1999CrossRefGoogle Scholar
  16. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L (2011) Microautophagy of cytosolic proteins by late endosomes. Dev Cell 20(1):131–139CrossRefGoogle Scholar
  17. Saksena S, Sun J, Chu T, Emr SD (2007) ESCRTing proteins in the endocytic pathway. Trends Biochem Sci 32(12):561–573CrossRefGoogle Scholar
  18. Salvador N, Aguado C, Horst M, Knecht E (2000) Import of a cytosolic protein into lysosomes by chaperone-mediated autophagy depends on its folding state. J Biol Chem 275(35):27447–27456PubMedGoogle Scholar
  19. Tekirdag K, Cuervo AM (2018) Chaperone-mediated autophagy and endosomal microautophagy: joint by a chaperone. J Biol Chem 293(15):5414–5424CrossRefGoogle Scholar
  20. Wang B, Cai Z, Tao K, Zeng W, Lu F, Yang R, Feng D, Gao G, Yang Q (2016) Essential control of mitochondrial morphology and function by chaperone-mediated autophagy through degradation of PARK7. Autophagy 12(8):1215–1228CrossRefGoogle Scholar
  21. Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z (2009) Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323(5910):124–127CrossRefGoogle Scholar

Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryTangdu Hospital, The Fourth Military Medical UniversityXi’anChina

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