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Autophagy is the natural, regulated mechanism of the cell that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components. Although initially characterised 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. 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.
Autophagin-1 (Atg4/Apg4) is a unique cysteine protease responsible for the cleavage of the carboxyl terminus of Atg8/Apg8/Aut7, a reaction essential for its lipidation during autophagy. Human Atg4 homologues cleave the carboxyl termini of the three human Atg8 homologues, microtubule-associated protein light chain 3 (LC3), GABARAP, and GATE-16.
Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.
Autophagy related 5 (ATG5) is a protein that, in humans, is encoded by the ATG5 gene located on Chromosome 6. It is an E3 ubi autophagic cell death. ATG5 is a key protein involved in the extension of the phagophoric membrane in autophagic vesicles. It is activated by ATG7 and forms a complex with ATG12 and ATG16L1. This complex is necessary for LC3-I conjugation to PE (phosphatidylethanolamine) to form LC3-II. ATG5 can also act as a pro-apoptotic molecule targeted to the mitochondria. Under low levels of DNA damage, ATG5 can translocate to the nucleus and interact with survivin.
Microtubule-associated proteins 1A/1B light chain 3B is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.
Microtubule-associated proteins 1A/1B light chain 3A is a protein that in humans is encoded by the MAP1LC3A gene. Two transcript variants encoding different isoforms have been found for this gene.
Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.
Autophagy-related protein 10 is a protein that in humans is encoded by the ATG10 gene.
Autophagy related 16 like 1 is a protein that in humans is encoded by the ATG16L1 gene.
Autophagy related 12 is a protein that in humans is encoded by the ATG12 gene.
WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene.
ULK1 is an enzyme that in humans is encoded by the ULK1 gene.
Autophagy related 7 is a protein in humans encoded by ATG7 gene. Related to GSA7; APG7L; APG7-LIKE.
Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals, this article mainly focuses on its role in lower eukaryotes such as Saccharomyces cerevisiae.
AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability.
An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents. After formation, autophagosomes deliver cytoplasmic components to the lysosomes. The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane.
Yoshinori Ohsumi is a Japanese cell biologist specializing in autophagy, the process that cells use to destroy and recycle cellular components. Ohsumi is a professor at Tokyo Institute of Technology's Institute of Innovative Research. He received the Kyoto Prize for Basic Sciences in 2012, the 2016 Nobel Prize in Physiology or Medicine, and the 2017 Breakthrough Prize in Life Sciences for his discoveries of mechanisms for autophagy.
Omegasome is a cell compartment consisting of lipid bilayer membranes enriched for phosphatidylinositol 3-phosphate and related to a process of autophagy. It is a subdomain of the endoplasmic reticulum (ER) membrane and has a morphology resembling Greek capital letter omega (Ω). Omegasomes are the sites from which phagophores form. Phagophores are sack-like structures that mature into autophagosomes that fuse with lysosomes in order to degrade the contents of the autophagosomes. The formation of omegasomes is increased as a response to starvation.
Autophagy related 9B is a protein that in humans is encoded by the ATG9B gene.
Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell, usually with a regulatory function. The UBL protein family derives its name from the first member of the class to be discovered, ubiquitin (Ub), best known for its role in regulating protein degradation through covalent modification of other proteins. Following the discovery of ubiquitin, many additional evolutionarily related members of the group were described, involving parallel regulatory processes and similar chemistry. UBLs are involved in a widely varying array of cellular functions including autophagy, protein trafficking, inflammation and immune responses, transcription, DNA repair, RNA splicing, and cellular differentiation.
References
- ↑ Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T (May 2008). "The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy". Mol. Biol. Cell. 19 (5): 2092–100. doi:10.1091/mbc.E07-12-1257. PMC 2366860 . PMID 18321988.
- ↑ Noda T, Fujita N, Yoshimori T (May 2008). "The Ubi brothers reunited". Autophagy. 4 (4): 540–1. doi: 10.4161/auto.5973 . PMID 18398292.
- ↑ Yamada Y, Suzuki NN, Hanada T, Ichimura Y, Kumeta H, Fujioka Y, Ohsumi Y, Inagaki F (March 2007). "The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation". J. Biol. Chem. 282 (11): 8036–43. doi: 10.1074/jbc.M611473200 . PMID 17227760.
- ↑ Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E (April 2002). "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p". J. Biol. Chem. 277 (16): 13739–44. doi: 10.1074/jbc.M200385200 . PMID 11825910.
- ↑ Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M (February 1997). "AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae". J. Bacteriol. 179 (4): 1068–76. doi:10.1128/jb.179.4.1068-1076.1997. PMC 178799 . PMID 9023185.
- ↑ Mizushima N, Yoshimori T, Ohsumi Y (December 2002). "Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method". FEBS Lett. 532 (3): 450–4. doi:10.1016/S0014-5793(02)03739-0. PMID 12482611. S2CID 37247321.
- ↑ Mizushima N, Yoshimori T, Ohsumi Y (May 2003). "Role of the Apg12 conjugation system in mammalian autophagy". Int. J. Biochem. Cell Biol. 35 (5): 553–61. doi:10.1016/S1357-2725(02)00343-6. PMID 12672448.