Omegasome

Omegasome is a cell organelle consisting of lipid bilayer membranes enriched for phosphatidylinositol 3-phosphate (abbreviated PI(3)P or PtdIns3P), and related to a process of autophagy.[1] It is a subdomain of the Endoplasmic Reticulum (ER),[2] and has a morphology resembling the Greek capital letter Omega (Ω). Omegasomes are the sites from which phagophores (also called "isolation membranes") form,[1][2] which are sack-like structures that mature into autophagosomes, and fuse with lysosomes in order to degrade the contents of the autophagosomes.[3] The formation of omegasomes depends on various factors, however in general, formation of omegasomes is increased as a response to starvation,[1] and in some biochemical situations the presence of PI(3)P leads to the formation of omegasomes.[4]

Figure from original paper, showing line diagrams of phagosomes arising from omegasomes (part D).

Macroautophagy
Illustration showing steps from omegasome to autolysosome.[5]

Autophagy (from Greek words for “self” and “eating”) is a process of digesting or degrading cytoplasmic molecules (proteins, lipids, sugars and organelles). Macroautophagy is the main autophagic pathway, used primarily to eradicate damaged cell organelles such as mitochondria,[6] ribosomes, etc., which helps in supplying amino acids and energy to the cells, and maintains longevity.[7] Omegasomes positioned on the endoplasmic reticulum, are enriched with PI(3)P and PI(3)P-binding proteins, and responsible for the formation of phagophores.[8] The omegasome is present at the opening of the sack-like phagophore while items destined for degradation by macroautophagy are loaded into the phagophore. There are specific receptor proteins that recruit items to the phagophore.[9] The phagophore expands to accommodate the items, until the omegasome is closed to produce the roughly spherical autophagosome. How autophagosomes are "detached" or "exit" from the omegasome is not clear, but autophagocytosis associated protein Atg3 and other proteins are required. Additionally, collections of thin tubules at the junction between omegasome and phagophore appear to be involved.[10] Actin is also believed to be important.[11][12] It has been observed that various pathogen infections that lead to the induction of autophagy display the formation of autophagosomes through omegasomes developed as an innate response to the infection.[13]

Function

Omegasomes display significant functional roles in different biochemical pathways which assist in various autophagosome processes. Omegasomes attract the effectors needed to target PI3P, while also ensuring that the autophagosomal membranes fuse with the double membrane vesicles and promote autophagosome formation.[4] Omegasomes act as progenitors of autophagosome formation during the autophagy pathway.[14] There are various autophagosome mediators involved in autophagy, however it is the omegasome regulation of the pathway that provides a smooth transition of autophagosome formation, and enrichment of nutrients in the cells.[14]

References
  1. Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, Griffiths G, Ktistakis NT, et al. (2008). "Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum". J Cell Biol. 182 (4): 685–701. doi:10.1083/jcb.200803137. PMC 2518708. PMID 18725538.
  2. Biazik J, Ylä-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL (2015). "Ultrastructural relationship of the phagophore with surrounding organelles". Autophagy. 11 (3): 439–51. doi:10.1080/15548627.2015.1017178. PMC 4502653. PMID 25714487.
  3. Kern A, Dikic I, Behl C (2015). "The integration of autophagy and cellular trafficking pathways via RAB GAPs". Autophagy. 11 (12): 2393–7. doi:10.1080/15548627.2015.1110668. PMC 4835203. PMID 26565612.
  4. Karanasios, Eleftherios; Stapleton, Eloise; Manifava, Maria; Kaizuka, Takeshi; Mizushima, Noboru; Walker, Simon A.; Ktistakis, Nicholas T. (2013-01-01). "Dynamic association of the ULK1 complex with omegasomes during autophagy induction". Journal of Cell Science. 126 (Pt 22): 5224–5238. doi:10.1242/jcs.132415. ISSN 1477-9137. PMID 24013547. S2CID 1195124.
  5. Kruppa AJ, Kendrick-Jones J, Buss F (2016). "Myosins, Actin and Autophagy". Traffic. 17 (8): 878–90. doi:10.1111/tra.12410. PMC 4957615. PMID 27146966.
  6. Yang JY, Yang WY (2013). "Bit-by-bit autophagic removal of parkin-labelled mitochondria". Nature Communications. 4: 2428. Bibcode:2013NatCo...4.2428Y. doi:10.1038/ncomms3428. PMID 24013556.
  7. Perrotta, Cristiana; Cattaneo, Maria Grazia; Molteni, Raffaella; De Palma, Clara (2020-12-10). "Autophagy in the Regulation of Tissue Differentiation and Homeostasis". Frontiers in Cell and Developmental Biology. 8: 602901. doi:10.3389/fcell.2020.602901. ISSN 2296-634X. PMC 7758408. PMID 33363161.
  8. Nascimbeni, Anna Chiara; Codogno, Patrice; Morel, Etienne (2017). "Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics". The FEBS Journal. 284 (9): 1267–1278. doi:10.1111/febs.13987. ISSN 1742-4658. PMID 27973739. S2CID 1796268.
  9. Kim BW, Kwon DH, Song HK (2016). "Structure biology of selective autophagy receptors". BMB Reports. 49 (2): 73–80. doi:10.5483/bmbrep.2016.49.2.265. PMC 4915120. PMID 26698872.
  10. Uemura T, Yamamoto M, Kametaka A, Sou YS, Yabashi A, Yamada A, Annoh H, Kametaka S, Komatsu M, Waguri S (2014). "A cluster of thin tubular structures mediates transformation of the endoplasmic reticulum to autophagic isolation membrane". Molecular and Cellular Biology. 34 (9): 1695–706. doi:10.1128/MCB.01327-13. PMC 3993601. PMID 24591649.
  11. Aguilera MO, Berón W, Colombo MI (2012). "The actin cytoskeleton participates in the early events of autophagosome formation upon starvation induced autophagy". Autophagy. 8 (11): 1590–603. doi:10.4161/auto.21459. PMC 3494589. PMID 22863730.
  12. Kruppa AJ, Kendrick-Jones J, Buss F (2016). "Myosins, Actin and Autophagy". Traffic. 17 (8): 878–90. doi:10.1111/tra.12410. PMC 4957615. PMID 27146966.
  13. Roberts, Rebecca; Ktistakis, Nicholas T. (2013-09-27). Lane, Jon D. (ed.). "Omegasomes: PI3P platforms that manufacture autophagosomes". Essays in Biochemistry. 55: 17–27. doi:10.1042/bse0550017. ISSN 0071-1365. PMID 24070468.
  14. Roberts, Rebecca; Ktistakis, Nicholas T. (2013-09-27). Lane, Jon D. (ed.). "Omegasomes: PI3P platforms that manufacture autophagosomes". Essays in Biochemistry. 55: 17–27. doi:10.1042/bse0550017. ISSN 0071-1365. PMID 24070468.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.