Skip to main content

History and Current Status of Autophagy Research

  • Chapter
  • First Online:
Autophagy: Biology and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1206))

Abstract

Autophagy is an evolutionarily conserved process in which eukaryotic bilayer membrane vesicles enclose intracellular contents and transport them to lysosomes for degradation. In the 1990s, Ohsumi et al. identified multiple autophagy-related genes in a yeast model. Functional homologues of almost all yeast autophagy-related genes were found in higher eukaryotes. In 2003, Klionsky et al. named these genes the Atg genes and studied the interactions between the proteins they encoded and their functions in autophagy. In April 2005, a new journal, Autophagy, was published that was edited by Klionsky. The number of autophagy research papers indexed by PubMed has increased each year. In 2016, Yoshinori Ohsumi won the Nobel Prize in Medicine or Physiology for his discovery of the autophagy mechanism. Autophagy has thus become a hot research area, which involves biology, medicine, botany and microbiology. Many researchers are actively exploring the relationship between non-selective and selective autophagy and various pathophysiological states in humans, and are studying the molecular mechanisms underlying autophagy regulation in various biological conditions, including cancer, neurodegenerative diseases, cardiovascular diseases, immune responses, development and ageing. This chapter focuses on the history and current status of autophagy research and highlights the milestones that contributed to the development of the field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Blommaart EF, Luiken JJ, Blommaart PJ, van Woerkom GM, Meijer AJ (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J Biol Chem 270:2320–2326

    Article  CAS  Google Scholar 

  • Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H, Huang L, Zhou C, Cai X, Fu C, Duan L, Wang X, Liu L, Liu X, Shen Y, Zhu Y, Chen Q (2014) A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 54:362–377

    Article  CAS  Google Scholar 

  • Fernandez AF, Sebti S, Wei Y, Zou Z, Shi M, McMillan KL, He C, Ting T, Liu Y, Chiang WC, Marciano DK, Schiattarella GG, Bhagat G, Moe OW, Hu MC, Levine B (2018) Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice. Nature 558:136–140

    Article  CAS  Google Scholar 

  • Garcia-Prat L, Martinez-Vicente M, Perdiguero E, Ortet L, Rodriguez-Ubreva J, Rebollo E, Ruiz-Bonilla V, Gutarra S, Ballestar E, Serrano AL, Sandri M, Munoz-Canoves P (2016) Autophagy maintains stemness by preventing senescence. Nature 529:37–42

    Article  CAS  Google Scholar 

  • Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:753–766

    Article  CAS  Google Scholar 

  • Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T (2013) Autophagosomes form at ER-mitochondria contact sites. Nature 495:389–393

    Article  CAS  Google Scholar 

  • Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889

    Article  CAS  Google Scholar 

  • Ho TT, Warr MR, Adelman ER, Lansinger OM, Flach J, Verovskaya EV, Figueroa ME, Passegue E (2017) Autophagy maintains the metabolism and function of young and old stem cells. Nature 543:205–210

    Article  CAS  Google Scholar 

  • Huang R, Xu Y, Wan W, Shou X, Qian J, You Z, Liu B, Chang C, Zhou T, Lippincott-Schwartz J, Liu W (2015) Deacetylation of nuclear LC3 drives autophagy initiation under starvation. Mol Cell 57:456–466

    Article  CAS  Google Scholar 

  • Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728

    Article  CAS  Google Scholar 

  • Khaminets A, Heinrich T, Mari M, Grumati P, Huebner AK, Akutsu M, Liebmann L, Stolz A, Nietzsche S, Koch N, Mauthe M, Katona I, Qualmann B, Weis J, Reggiori F, Kurth I, Hubner CA, Dikic I (2015) Regulation of endoplasmic reticulum turnover by selective autophagy. Nature 522:354–358

    Article  CAS  Google Scholar 

  • Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132–141

    Article  CAS  Google Scholar 

  • Klionsky DJ, Cregg JM, Dunn WA, Emr SD, Sakai Y, Sandoval IV, Sibirny A, Subramani S, Thumm M, Veenhuis M, Ohsumi Y (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5, 539–545

    Article  CAS  Google Scholar 

  • Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524:309–314

    Article  CAS  Google Scholar 

  • Levine B, Klionsky DJ (2017) Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker’s yeast fuel advances in biomedical research. Proc Natl Acad Sci USA 114:201–205

    Article  CAS  Google Scholar 

  • Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402:672–676

    Article  CAS  Google Scholar 

  • Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185

    Article  Google Scholar 

  • Mizushima N (2018) A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol 20:521–527

    Article  CAS  Google Scholar 

  • Mizushima N, Noda T, Yoshimori T, Tanaka Y, Ishii T, George MD, Klionsky DJ, Ohsumi M, Ohsumi Y (1998) A protein conjugation system essential for autophagy. Nature 395:395–398

    Article  CAS  Google Scholar 

  • Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111

    Article  CAS  Google Scholar 

  • Mochida K, Oikawa Y, Kimura Y, Kirisako H, Hirano H, Ohsumi Y, Nakatogawa H (2015) Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus. Nature 522:359–362

    Article  CAS  Google Scholar 

  • Mortimore GE, Schworer CM (1977) Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 270:174–176

    Article  CAS  Google Scholar 

  • Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939

    Article  CAS  Google Scholar 

  • Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454:232–235

    Article  CAS  Google Scholar 

  • Schuck S, Gallagher CM, Walter P (2014) ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery. J Cell Sci 127:4078–4088

    Article  CAS  Google Scholar 

  • Seglen PO, Gordon PB (1982) 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A 79:1889–1892

    Article  CAS  Google Scholar 

  • Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ (2009) Autophagy regulates lipid metabolism. Nature 458:1131–1135

    Article  CAS  Google Scholar 

  • Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (1992) Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119:301–311

    Article  CAS  Google Scholar 

  • Wang Y, Zhang N, Zhang L, Li R, Fu W, Ma K, Li X, Wang L, Wang J, Zhang H, Gu W, Zhu WG, Zhao Y (2016) Autophagy regulates chromatin ubiquitination in DNA damage response through elimination of SQSTM1/p62. Mol Cell 63:34–48

    Article  CAS  Google Scholar 

  • Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, Qian Y, Kryczek I, Sun D, Nagarsheth N, Chen Y, Chen H, Hong J, Zou W, Fang JY (2017) Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170(548–563):e16

    Google Scholar 

  • Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965

    Article  CAS  Google Scholar 

  • Zhang G, Wang Z, Du Z, Zhang H (2018) mTOR regulates phase separation of PGL granules to modulate their autophagic degradation. Cell 174(1492–1506):e22

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Rui Sheng or Zheng-Hong Qin .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Science Press and Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sheng, R., Qin, ZH. (2019). History and Current Status of Autophagy Research. 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_1

Download citation

Publish with us

Policies and ethics