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Autophagy information


Not to be confused with Autophagia.
This article is about the cellular process. For other uses, see Autophagy (disambiguation).
A Diagram of the process of autophagy, which produces the structures autophagosomes (AP), and autolysosomes (AL); B Electron micrograph of autophagic structures AP and AL in the fat body of a fruit fly larva; C Fluorescently-labeled autophagosomes AP in liver cells of starved mice.

Autophagy (or autophagocytosis; from the Ancient Greek αὐτόφαγος, autóphagos, meaning "self-devouring"[1] and κύτος, kýtos, meaning "hollow")[2] is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism.[3] It allows the orderly degradation and recycling of cellular components.[4][5] Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells.[6] Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly.[6][7]

Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy.[8][9][10] In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components (like mitochondria) are targeted and isolated from the rest of the cell within a double-membrane vesicle known as an autophagosome,[11][12] which, in time, fuses with an available lysosome, bringing its specialty process of waste management and disposal; and eventually the contents of the vesicle (now called an autolysosome) are degraded and recycled. In crinophagy (the least well-known and researched form of autophagy), unnecessary secretory granules are degraded and recycled.[8]

In disease, autophagy has been seen as an adaptive response to stress, promoting survival of the cell; but in other cases, it appears to promote cell death and morbidity. In the extreme case of starvation, the breakdown of cellular components promotes cellular survival by maintaining cellular energy levels.

The word "autophagy" was in existence and frequently used from the middle of the 19th century.[13] In its present usage, the term autophagy was coined by Belgian biochemist Christian de Duve in 1963 based on his discovery of the functions of lysosome.[3] The identification of autophagy-related genes in yeast in the 1990s allowed researchers to deduce the mechanisms of autophagy,[14][15][16][17][18] which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.[19]

  1. ^ Liddell HG, Scott R, Jone HS. "αὐτό-φαγος". A Greek–English Lexicon. tufts.edu. Retrieved 6 September 2018.
  2. ^ Liddell HG, Scott R, Jone HS. "κύτος". A Greek–English Lexicon. tufts.edu. Retrieved 6 September 2018.
  3. ^ a b Klionsky DJ (August 2008). "Autophagy revisited: a conversation with Christian de Duve". Autophagy. 4 (6): 740–3. doi:10.4161/auto.6398. PMID 18567941. S2CID 6198427.
  4. ^ Mizushima N, Komatsu M (November 2011). "Autophagy: renovation of cells and tissues". Cell. 147 (4): 728–41. doi:10.1016/j.cell.2011.10.026. PMID 22078875.
  5. ^ Kobayashi S (2015). "Choose Delicately and Reuse Adequately: The Newly Revealed Process of Autophagy". Biological & Pharmaceutical Bulletin. 38 (8): 1098–103. doi:10.1248/bpb.b15-00096. PMID 26235572.
  6. ^ a b Djajadikerta A, Keshri S, Pavel M, Prestil R, Ryan L, Rubinsztein DC (April 2020). "Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases". Journal of Molecular Biology. 432 (8): 2799–2821. doi:10.1016/j.jmb.2019.12.035. PMID 31887286. S2CID 209518157.
  7. ^ Levy JM, Towers CG, Thorburn A (September 2017). "Targeting autophagy in cancer". Nature Reviews. Cancer. 17 (9): 528–542. doi:10.1038/nrc.2017.53. PMC 5975367. PMID 28751651.
  8. ^ a b Csizmadia T, Juhász G (2020). "Crinophagy mechanisms and its potential role in human health and disease". Autophagy in health and disease. Progress in Molecular Biology and Translational Science. Vol. 172. pp. 239–255. doi:10.1016/bs.pmbts.2020.02.002. ISBN 9780128220214. PMID 32620244. S2CID 212903191.
  9. ^ Parzych, Katherine R.; Klionsky, Daniel J. (2014-01-20). "An Overview of Autophagy: Morphology, Mechanism, and Regulation". Antioxidants & Redox Signaling. 20 (3): 460–473. doi:10.1089/ars.2013.5371. ISSN 1523-0864. PMC 3894687. PMID 23725295.
  10. ^ Hill, Rhianna Mae; Fok, Matthew; Grundy, Gabrielle; Parsons, Jason Luke; Rocha, Sonia (2023-10-11). "The role of autophagy in hypoxia-induced radioresistance". Radiotherapy and Oncology. 189: 109951. doi:10.1016/j.radonc.2023.109951. ISSN 0167-8140. PMID 37838322. S2CID 264073704.
  11. ^ Mizushima N, Yoshimori T, Ohsumi Y (10 November 2011). "The role of Atg proteins in autophagosome formation". Annual Review of Cell and Developmental Biology. 27 (1): 107–32. doi:10.1146/annurev-cellbio-092910-154005. PMID 21801009.
  12. ^ Xie Z, Klionsky DJ (October 2007). "Autophagosome formation: core machinery and adaptations". Nature Cell Biology. 9 (10): 1102–9. doi:10.1038/ncb1007-1102. PMID 17909521. S2CID 26402002.
  13. ^ Ktistakis NT (2017). "In praise of M. Anselmier who first used the term "autophagie" in 1859". Autophagy. 13 (12): 2015–2017. doi:10.1080/15548627.2017.1367473. PMC 5788564. PMID 28837378.
  14. ^ Klionsky DJ, Cueva R, Yaver DS (October 1992). "Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway". The Journal of Cell Biology. 119 (2): 287–99. doi:10.1083/jcb.119.2.287. PMC 2289658. PMID 1400574.
  15. ^ Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y (October 1992). "Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction". The Journal of Cell Biology. 119 (2): 301–11. doi:10.1083/jcb.119.2.301. PMC 2289660. PMID 1400575.
  16. ^ Thumm M, Egner R, Koch B, Schlumpberger M, Straub M, Veenhuis M, Wolf DH (August 1994). "Isolation of autophagocytosis mutants of Saccharomyces cerevisiae". FEBS Letters. 349 (2): 275–80. doi:10.1016/0014-5793(94)00672-5. PMID 8050581. S2CID 26072787.
  17. ^ Tsukada M, Ohsumi Y (October 1993). "Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae". FEBS Letters. 333 (1–2): 169–74. doi:10.1016/0014-5793(93)80398-e. PMID 8224160. S2CID 46017791.
  18. ^ Harding TM, Morano KA, Scott SV, Klionsky DJ (November 1995). "Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway". The Journal of Cell Biology. 131 (3): 591–602. doi:10.1083/jcb.131.3.591. PMC 2120622. PMID 7593182.
  19. ^ "The Nobel Prize in Physiology or Medicine 2016". The Nobel Foundation. 3 October 2016. Retrieved 3 October 2016.

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endocytosis, while material from the inside of the cell is digested through autophagy. The sizes of the organelles vary greatly—the larger ones can be more...

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MTOR

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cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions...

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organism of which the cells are part. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis...

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