Omegasome
Omegasome is a cell membrane compartment consisted mostly of PI(3)P formed after starvation and related to a process of autophagy.
Omegasomes
Omegasomes rise from endoplasmic reticulum (ER) membrane after amino acid starvation and have a typical morphology resembling Greek capital letter omega (Ω). Their membranes are strongly enriched of phosphatidylinositol (3,4,5)-trisphosphate (PI(3)P). [1]
Omegasomes and autophagy
Autophagy (from Latin words for “self” and “eating”) is a process of digesting or degrading cytoplasmic molecules (proteins, lipids, sugars and organelles) self to the cell and it has a variety of physiological functions such as response to starvation, clearance of cytoplasmic molecules and other immunologic and tumor suppression functions. Three different types of autophagosomes pathways to lysosomes have been depicted called macroautophagy (or simply autophagy), microautophagy and chaperone-mediated autophagy. Macroautophagy include the process of formation of autophagosomes, while microautophagy is sequestering of cytoplasm by lysosome itself and chaperone-mediated autophagy degrades only proteins including specific-signal sequence. [2][3]
After macroautophagy induction omegasomes are derived from ER and serve as intermediates for genesis of isolation membrane (also called autophagosome phagophore or preautophagosome) from ER cisternae membranes. They form a cradle for the formation of phagophore by membrane invagination. While the isolation membrane expands to engulf cytoplasmic components it is encircled or sandwiched by omegasome to the time the membrane is sealed and forms a double-membrane autophagosome. This process resembles the creation of bubble by bubble gum. How autophagosome exits the omegasome is not clear so far.[1][2][3][4]
Autophagic specific mTor signaling pathway is activated by ULK1/Atg13/FIP200/Atg101 kinase complex. Double FYVE-domain containing protein 1 (DFCP1) which bounds PI(3)P translocates to newly forming parts of ER with enriched occurrence of PI(3)P called omegasomes. The formation process of omegasomes is regulated positively by Atg14/Vps34/beclin1 PI3-kinase complex and negatively by PI(3)P phosphatases Jumpy/MTMR14 and MTMR3. Then the isolation membrane is formed in the center of the ring of omegasome. Complexes ULK1/Atg13/FIP200/Atg101, Atg14/Vps34/beclin1, Atg12/Atg5/Atg16 and protein mAtg9 are recruited to the isolation membrane and the elongation step involving engulfing of cytoplasmic components begins. [1][3][4] [5][6]
References
- ^ a b c Axe EL, Walker SA, Manifava M, Chandra P, Roderick; 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. PMID 18725538.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ a b Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T; et al. (2009). "A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation". Nat Cell Biol. 11 (12): 1433–7. doi:10.1038/ncb1991. PMID 19898463.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ a b c Tanida I (2011). "Autophagosome Formation and Molecular Mechanism of Autophagy". Antioxid Redox Signal. 14 (11): 2201–14. doi:10.1089/ars.2010.3482. PMID 20712405.
- ^ a b Tanida I (2011). "Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate". Autophagy. 7 (11): 1335–47. doi:10.4161/auto.7.11.16642. PMID 21799305.
- ^ Simonsen A, Stenmark H (2008). "Self-eating from an ER-associated cup". J Cell Biol. 182 (4): 621–2. doi:10.1083/jcb.200807061. PMID 18725534.
- ^ Noda T. Matsanaga K, Yoshimori T (2011). "Atg14L recruits PtdIns 3-kinase to the ER for autophagosome formation". Autophagy. 7 (4): 438–9. PMID 21228623.