LC3 conjugation system in mammalian autophagy

By I. Tanida, T. Ueno, E. Kominami. International Journal of Biochemistry and Cell Biology, 2004

1,489 citations recorded by the source corpus.

Autophagy is the bulk degradation of proteins and organelles, a process essential for cellular maintenance, cell viability, differentiation and development in mammals. Autophagy has significant associations with neurodegenerative diseases, cardiomyopathies, cancer, programmed cell death, and bacterial and viral infections. During autophagy, a cup-shaped structure, the preautophagosome, engulfs cytosolic components, including organelles, and closes, forming an autophagosome, which subsequently fuses with a lysosome, leading to the proteolytic degradation of internal components of the autophagosome by lysosomal lytic enzymes. During the formation of mammalian autophagosomes, two ubiquitylation-like modifications are required, Atg12-conjugation and LC3-modification. LC3 is an autophagosomal ortholog of yeast Atg8. A lipidated form of LC3, LC3-II, has been shown to be an autophagosomal marker in mammals, and has been used to study autophagy in neurodegenerative and neuromuscular diseases, tumorigenesis, and bacterial and viral infections. The other Atg8 homologues, GABARAP and GATE-16, are also modified by the same mechanism. In non-starved rats, the tissue distribution of LC3-II differs from those of the lipidated forms of GABARAP and GATE-16, GABARAP-II and GATE-16-II, suggesting that there is a functional divergence among these three modified proteins. Delipidation of LC3-II and GABARAP-II is mediated by hAtg4B. We review the molecular mechanism of LC3-modification, the crosstalk between LC3-modification and mammalian Atg12-conjugation, and the cycle of LC3-lipidation and delipidation mediated by hAtg4B, as well as recent findings concerning the other two Atg8 homologues, GABARAP and GATE-16. We also highlight recent findings regarding the pathobiology of LC3-modification, including its role in microbial infection, cancer and neuromuscular diseases.

Subfields: Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/7fed8bdcadce6f111f07b8f4d6a327782a46f66e

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Citations in the corpus

Glycogen and its metabolism: some new developments and old themes. (2012, background): “In mammals, the situation is more complex as there are six orthologues of Atg8, the best studied being LC3 (light chain 3), whose lipidation is often used as a marker for autophagy induced by nutritional stresses [236].”
Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. (2006, background): “AKT inhibits autophagy-mediated survival in ischemia To quantitate the level of autophagy induced by ischemia in D3 compared to D3 AKT cells, cytosol to membrane translocation of the autophagy marker EGFP-LC3 was monitored (Mizushima et al., 2004; Tanida et al., 2004).”
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy (2022, background): “During LC3 lipidation, LC3 is sheared to the soluble form LC3I as the precursor of LC3II which is a docking site covalently attaching to the membrane of phagosomes for cargo receptors.(48,56,57) The receptor binds to specific cargoes through ubiquitin labeling, which is central to the selective recr”
Oxidative Stress and Autophagy (2006, neutral): “These markers are now used fused to fluorescent proteins or detected directly with antibodies conjugated to gold particles in immunoelectron microscopy (53, 71).”
Autophagy during viral infection — a double-edged sword (2018, background): “another uBL molecule, LC3, is cleaved by the atG4 protease at its C-terminal arginine to expose a glycine residue(161) and is subjected to a second uBL conjugation reaction involving atG7 and atG3 (ReF.(162)).”
Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer's Disease (2008, background): “These results indicate that neurons initiate and sustain autophagy induction when mTOR is inhibited; however, they do not accumulate large numbers of autophagosomes, which are efficiently converted to autolysosomes by lysosomal hydrolases (Tanida et al., 2004).”
The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. (2010, background): “Genetic screens in yeast have identified more than 30 autophagy-related genes (ATGs) (26), many of which have known homologs in mammalian cells.”
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG (2006, background): “During autophagy, the LC3 precursor (LC3-I) undergoes cleavage and lipidation to a processed form (LC3-II”
Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains (2009, background): “amino acid starvation, the LC3-I protein localized in the cytoplasm is cleaved, lipidated, and inserted as LC3-II into autophagosome membranes (36).”