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Autophagy and the Metabolism of Misfolding Protein

  • Chao ChengEmail author
  • Zhen-Guo Liu
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1206)

Abstract

Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. An increasing number of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models and human diseases were carried out. Among them, the clearance of misfolded proteins is the important function of autophagy. Impairment at different steps of the autophagy system, such as the ubiquitin-proteasome and the autophagy-lysosome pathways, may result in the accumulation of misfolded proteins in insoluble aggregates. Abnormal accumulation of misfolded proteins in cells can lead to a variety of human diseases. Here, we review the major advances in autophagy and the metabolism of misfolding protein in human diseases. Current studies about the promising therapeutic strategy in autophagy-modulating are also summarized.

Keywords

Autophagy Misfolding protein Metabolism Aggregation 

References

  1. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805–810CrossRefGoogle Scholar
  2. Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368:651–662CrossRefGoogle Scholar
  3. Cipolat Mis MS, Brajkovic S, Frattini E, Di Fonzo A, Corti S (2016) Autophagy in motor neuron disease: key pathogenetic mechanisms and therapeutic targets. Mol Cell Neurosci 72:84–90CrossRefGoogle Scholar
  4. Daw NC, Chou AJ, Jaffe N, Rao BN, Billups CA, Rodriguez-Galindo C, Meyers PA, Huh WW (2015) Recurrent osteosarcoma with a single pulmonary metastasis: a multi-institutional review. Br J Cancer 112:278–282CrossRefGoogle Scholar
  5. Evans CS, Holzbaur ELF (2019) Autophagy and mitophagy in ALS. Neurobiol Dis 122:35–40CrossRefGoogle Scholar
  6. Finn PF, Mesires NT, Vine M, Dice JF (2005) Effects of small molecules on chaperone-mediated autophagy. Autophagy 1:141–145CrossRefGoogle Scholar
  7. Jiang P, Mizushima N (2014) Autophagy and human diseases. Cell Res 24:69–79CrossRefGoogle Scholar
  8. Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, Ogawa S, Kaufman RJ, Kominami E, Momoi T (2007) ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 14:230–239CrossRefGoogle Scholar
  9. Kubota H (2009) Quality control against misfolded proteins in the cytosol: a network for cell survival. J Biochem 146:609–616CrossRefGoogle Scholar
  10. Martin DD, Ladha S, Ehrnhoefer DE, Hayden MR (2015) Autophagy in Huntington disease and huntingtin in autophagy. Trends Neurosci 38:26–35CrossRefGoogle Scholar
  11. Martinez-Vicente M, Cuervo AM (2007) Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol 6:352–361CrossRefGoogle Scholar
  12. Menzies FM, Moreau K, Rubinsztein DC (2011) Protein misfolding disorders and macroautophagy. Curr Opin Cell Biol 23:190–197CrossRefGoogle Scholar
  13. Metcalf DJ, Garcia-Arencibia M, Hochfeld WE, Rubinsztein DC (2012) Autophagy and misfolded proteins in neurodegeneration. Exp Neurol 238:22–28CrossRefGoogle Scholar
  14. Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, Diprospero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao TP, Baehrecke EH, Taylor JP (2007) HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447:859–863CrossRefGoogle Scholar
  15. Ramesh N, Pandey UB (2017) Autophagy dysregulation in ALS: when protein aggregates get out of hand. Front Mol Neurosci 10:263CrossRefGoogle Scholar
  16. Rubinsztein DC, Difiglia M, Heintz N, Nixon RA, Qin ZH, Ravikumar B, Stefanis L, Tolkovsky A (2005) Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy 1:11–22CrossRefGoogle Scholar
  17. Scrivo A, Bourdenx M, Pampliega O, Cuervo AM (2018) Selective autophagy as a potential therapeutic target for neurodegenerative disorders. Lancet Neurol 17:802–815CrossRefGoogle Scholar
  18. Senft D, Ronai ZA (2015) UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends Biochem Sci 40:141–148CrossRefGoogle Scholar
  19. Sheehan P, Yue Z (2019) Deregulation of autophagy and vesicle trafficking in Parkinson’s disease. Neurosci Lett 697:59–65CrossRefGoogle Scholar
  20. Szeto J, Kaniuk NA, Canadien V, Nisman R, Mizushima N, Yoshimori T, Bazett-Jones DP, Brumell JH (2006) ALIS are stress-induced protein storage compartments for substrates of the proteasome and autophagy. Autophagy 2:189–199CrossRefGoogle Scholar
  21. Tabone MD, Kalifa C, Rodary C, Raquin M, Valteau-Couanet D, Lemerle J (1994) Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol 12:2614–2620CrossRefGoogle Scholar

Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Thoracic SurgeryThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China

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