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.
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References
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):825–834
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):1464–1472
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):382–385
Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273(5274):501–503
Cuervo AM, Wong E (2014) Chaperone-mediated autophagy: roles in disease and aging. Cell Res 24(1):92–104
Dice JF (1990) Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends Biochem Sci 15(8):305–309
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):15–26
Finn PF, Dice JF (2005) Ketone bodies stimulate chaperone-mediated autophagy. J Biol Chem 280(27):25864–25870
Kaushik S, Cuervo AM (2018) The coming of age of chaperone-mediated autophagy. Nat Rev Mol Cell Biol 19(6):365–381
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):109ra117
Li WW, Li J, Bao JK (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69(7):1125–1136
Li W, Nie T, Xu H, Yang J, Yang Q, Mao Z (2019) Chaperone-mediated autophagy: advances from bench to bedside. Neurobiol Dis 12241–48
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):719–730
Mijaljica D, Prescott M, Devenish RJ (2011) Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7(7):673–682
Mukherjee A, Patel B, Koga H, Cuervo AM, Jenny A (2016) Selective endosomal microautophagy is starvation-inducible in Drosophila. Autophagy 12(11):1984–1999
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):131–139
Saksena S, Sun J, Chu T, Emr SD (2007) ESCRTing proteins in the endocytic pathway. Trends Biochem Sci 32(12):561–573
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):27447–27456
Tekirdag K, Cuervo AM (2018) Chaperone-mediated autophagy and endosomal microautophagy: joint by a chaperone. J Biol Chem 293(15):5414–5424
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):1215–1228
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):124–127
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Yang, Q., Wang, R., Zhu, L. (2019). Chaperone-Mediated Autophagy. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_20
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DOI: https://doi.org/10.1007/978-981-15-0602-4_20
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