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Molecular dissection of autophagy: two ubiquitin-like systems
Abstract
Recent analyses of the genes required for autophagy--intracellular bulk protein degradation--in yeast have revealed two ubiquitin-like systems, both of which are involved in the membrane dynamics of the process. Molecular dissection of these systems is now revealing some surprises.
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“One universal activator of autophagy is a decrease in nutrient availability and this stimulation occurs, at least in part, by the inhibition of TOR (target of rapamycin) signalling 74 .”
From The common biology of cancer and ageing (2007) · cites this paper as [74]
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“ubiquitin-like (Ubl) conjugation systems that involve Ubl proteins Atg12 and Atg8 that share structural similarity to ubiquitin but are not genuine homologs [reviewed in [24]].”
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“In the Atg12–Atg5 conjugation system, Atg7, which acts as an E1 ubiquitin-activating enzyme (46), and Atg10, which functions like an E2 ubiquitin-conjugating enzyme (83), are required, where Atg7 binds to Atg12, which is in turn activated by ATP hydrolysis, transferred to Atg10, and then conjugated with Atg5.”
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“LC3 is then activated by Atg7 (E1 enzyme) and transferred to Atg3 (E2 enzyme), and the Atg12-5-16L1 complex (E3 enzyme) facilitates the transfer of LC3 from Atg3 to phosphatidylethanolamine (PE) (Atg8/LC3 lipidation) [130].”
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“The outer membrane of a mature autophagosome fuses with the lysosome (in mammals) or vacuole (in yeast and plants) to release the sequestered cargo for breakdown by acid hydrolases (Mizushima et al., 2008; Ohsumi, 2001).”
BackgroundProtein kinase C inhibits autophagy and phosphorylates LC3
Jiang, H., Cheng, D., Liu, W., Peng, J., & Feng, J. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.04.030 · Cited by 99
“The molecular basis of autophagy has been extensively studied in yeast [3].”
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“Beclin1 and Atg5 are essential proteins required for the initiation of autophagosome formation (21).”
Macroautophagy Signaling and Regulation
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Mitochondrial Extrusion through the Cytoplasmic Vacuoles during Cell Death
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“Biology 121, 305-315 10 Ohsumi, Y. (2001) Molecular dissection of”
BackgroundThe unfolded protein response regulates hepatic autophagy by sXBP1-mediated activation of TFEB
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“Also key to cellular metabolic adaptation is macroautophagy/ autophagy, a conserved catabolic process whereby organelles and components of the cytoplasm are degraded within lysosomes [15].”
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“A group of genes known as ATG genes, which are conserved from yeast to humans, has been found to control autophagy [17].”
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“…endoplasmic reticulum, peroxisomes, and lysosomes) as well as cytotoxic protein aggregates from the cell, promoting overall survival (Ravikumar et al., 2002; Rodriguez-Enriquez et al., 2004; Bernales et al., 2006; Iwata et al., 2006; Høyer-Hansen and Jaattela, 2007; Ostenfeld et al., 2008).”
BackgroundAutophagy in Brain Tumors: A New Target for Therapeutic Intervention
Kaza, N., Kohli, L., & Roth, K. A. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00544.x · Cited by 98
“Vesicle elongation involves two ubiquitin-like conjugation systems (66, 67).”
BackgroundChloroquine-Induced Neuronal Cell Death Is p53 and Bcl-2 Family-Dependent But Caspase-Independent
Zaidi, A. U., McDonough, J. S., Klocke, B. J., Latham, C. B., Korsmeyer, S. J., Flavell, R. A., Schmidt, R. E., & Roth, K. A. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.10.937 · Cited by 95
Processing of autophagic protein LC3 by the 20S proteasome
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“These reactions are conjugation of ATG12 to ATG5 and conjugation of ATG8/LC3 to phosphatidylethanolamine (PE).(20-22)”
BackgroundDihydroartemisinin induces autophagy by suppressing NF-κB activation
Hu, W., Chen, S.-S., Zhang, J., Lou, X.-E., & Zhou, H. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.09.035 · Cited by 95
“The formation of autophagosomes requires the involvement of 2 ubiquitin-like conjugation systems (ATG 5ATG 12 and LC3 lipidation) [6].”
BackgroundHBx induces HepG-2 cells autophagy through PI3K/Akt–mTOR pathway
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“3) (Ohsumi 2001).”
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Crosstalk between apoptosis and autophagy signaling pathways
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Rapamycin regulates autophagy and cell adhesion in induced pluripotent stem cells
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“They regulate autophagosome formation through two evolutionarily conserved ubiquitin-like conjugation systems, the ATG12–ATG5 and the ATG8 (LC3)– PE (phosphatidylethanolamine) systems [16].”
Metadata
- Authors
- Ohsumi, Y.
- Affiliations
- National Institute for Basic Biology (JP)
- Corresponding author
- Ohsumi, Yoshinori
- ORCID
- Ohsumi, Yoshinori
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2001-03
- Volume
- 2
- Issue
- 3
- Pages
- 211-216
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2792139654
- Cited by
- 1,240
- References
- 45
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 30 · 2023: 44 · 2022: 39 · 2021: 34 · 2020: 64 · 2019: 65 · 2018: 51 · 2017: 54 · 2016: 59 · 2015: 44 · 2014: 58 · 2013: 56 · 2012: 67
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- autophagy, ubiquitin-like proteins, membrane dynamics, yeast, autophagy-related genes
- MeSH terms
- Autophagy-Related Protein 8 Family, Autophagy-Related Protein 7, Autophagy, Lysosomes, Microscopy, Electron, Microtubule-Associated Proteins, Models, Biological, Proteins, Saccharomyces cerevisiae, Ubiquitins, Vacuoles, Saccharomyces cerevisiae Proteins
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