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Gene Review

ATG8  -  ubiquitin-like protein ATG8

Saccharomyces cerevisiae S288c

Synonyms: APG8, AUT7, Autophagy-related protein 8, Autophagy-related ubiquitin-like modifier ATG8, CVT5, ...
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High impact information on ATG8


Biological context of ATG8

  • To evaluate this requirement, we examined the ubiquitination-like Atg8 lipidation system, whose component genes are all found in the Arabidopsis genome [3].
  • However, the apg7-1 mutant is hypersensitive to nutrient limiting conditions and displays premature leaf senescence. mRNAs for both APG7 and APG8 preferentially accumulate as leaves senesce, suggesting that both conjugation pathways are up-regulated during the senescence syndrome [4].
  • Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy [5].
  • When LC3A and LC3B were overexpressed, both exhibited two forms (18 and 16 kDa, representing types of I and II, separately), which might be due to post-translational modification including the characteristic C-terminal cleavage at these two proteins as similar to that found in rat LC3 and yeast Atg8 [6].
  • Atg4B, a mammalian homologue of yeast Atg4, has been shown to play an important role in the processing of LC3, a mammalian homologue of yeast Atg8, but the tissue distribution of Atg4B remains unknown [7].

Anatomical context of ATG8

  • Our findings suggest that microtubules and an attached protein complex of Aut2p and Aut7p are involved in the delivery of autophagic vesicles to the vacuole [8].
  • In vivo, AUT7 interacts genetically with endoplasmic reticulum to Golgi SNAREs, specifically with BET1 and SEC22 [9].
  • In both pathways, the vesicle formation process requires the function of the starvation-induced Aut7 protein, which is recruited from the cytosol to the forming Cvt vesicles and autophagosomes [2].
  • We show here that the nature of the association of Apg8 with membranes changes depending on a series of modifications of the protein itself [10].
  • Along these lines, we demonstrate that Berkeley bodies, a structure generated from the Golgi complex in sec7 cells, are immunolabeled with Atg8, a structural component of autophagosomes [11].

Associations of ATG8 with chemical compounds

  • First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG [10].
  • We show that these two sites are associated with different functions of Atg8: Phe 77 and Phe 79 seem to be part of the recognition site for Atg4, a cystein protease that acts also as a deubiquitination enzyme, whereas Tyr 49 and Leu 50 act downstream of the lipidation step [12].
  • CONCLUSIONS: Sucrose starvation induces autophagy and up-regulates orthologues of the yeast Atg8 conjugation pathway genes in Arabidopsis cultured cells [13].
  • Selective vacuolar targeting of the autophagosomal marker GFP-Aut7 and the accumulation of autophagic bodies during starvation in the presence of phenylmethylsulfonyl fluoride suggest that autophagy occurs in atg23Delta cells but at a reduced rate [14].
  • Atg3 is an E2-like enzyme that catalyzes the conjugation reaction between Atg8 and phosphatidylethanolamine (PE) [15].

Enzymatic interactions of ATG8

  • After synthesis in the cytosol, Aut7p is proteolytically cleaved in an Aut2p-dependent manner [2].

Regulatory relationships of ATG8

  • These data suggest that Aut7p is induced during autophagy and delivered to the vacuole together with precursor API by Cvt/autophagic vesicles [16].

Other interactions of ATG8

  • In this study, we characterize mutations in the putative Dictyostelium discoideum orthologues of budding yeast genes that are involved in one of each of these functions, ATG1, ATG6, and ATG8 [17].
  • Autophagic nutrient recycling in Arabidopsis directed by the ATG8 and ATG12 conjugation pathways [18].
  • The distribution of a green fluorescent protein fusion of the autophagosome marker, Atg8, is aberrant in both atg1-1 and atg6(-) mutants [17].
  • Using an Arabidopsis (Arabidopsis thaliana) atg7 mutant unable to ligate either tag, we previously showed that the ATG8/12 conjugation system is important for survival under nitrogen-limiting growth conditions [18].
  • Finally, the aut7/cvt5 mutant accumulates precursor API at a stage prior to vesicle completion [16].

Analytical, diagnostic and therapeutic context of ATG8


  1. A ubiquitin-like system mediates protein lipidation. Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T., Ohsumi, Y. Nature (2000) [Pubmed]
  2. Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex. Kim, J., Huang, W.P., Klionsky, D.J. J. Cell Biol. (2001) [Pubmed]
  3. Processing of ATG8s, ubiquitin-like proteins, and their deconjugation by ATG4s are essential for plant autophagy. Yoshimoto, K., Hanaoka, H., Sato, S., Kato, T., Tabata, S., Noda, T., Ohsumi, Y. Plant Cell (2004) [Pubmed]
  4. The APG8/12-activating enzyme APG7 is required for proper nutrient recycling and senescence in Arabidopsis thaliana. Doelling, J.H., Walker, J.M., Friedman, E.M., Thompson, A.R., Vierstra, R.D. J. Biol. Chem. (2002) [Pubmed]
  5. Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy. Strømhaug, P.E., Reggiori, F., Guan, J., Wang, C.W., Klionsky, D.J. Mol. Biol. Cell (2004) [Pubmed]
  6. Molecular cloning and characterization of rat LC3A and LC3B--two novel markers of autophagosome. Wu, J., Dang, Y., Su, W., Liu, C., Ma, H., Shan, Y., Pei, Y., Wan, B., Guo, J., Yu, L. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  7. Effects of RNA Interference of Atg4B on the Limited Proteolysis of LC3 in PC12 Cells and Expression of Atg4B in Various Rat Tissues. Yoshimura, K., Shibata, M., Koike, M., Gotoh, K., Fukaya, M., Watanabe, M., Uchiyama, Y. Autophagy. (2006) [Pubmed]
  8. Aut2p and Aut7p, two novel microtubule-associated proteins are essential for delivery of autophagic vesicles to the vacuole. Lang, T., Schaeffeler, E., Bernreuther, D., Bredschneider, M., Wolf, D.H., Thumm, M. EMBO J. (1998) [Pubmed]
  9. Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. Legesse-Miller, A., Sagiv, Y., Glozman, R., Elazar, Z. J. Biol. Chem. (2000) [Pubmed]
  10. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. Kirisako, T., Ichimura, Y., Okada, H., Kabeya, Y., Mizushima, N., Yoshimori, T., Ohsumi, M., Takao, T., Noda, T., Ohsumi, Y. J. Cell Biol. (2000) [Pubmed]
  11. Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Reggiori, F., Wang, C.W., Nair, U., Shintani, T., Abeliovich, H., Klionsky, D.J. Mol. Biol. Cell (2004) [Pubmed]
  12. Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy. Amar, N., Lustig, G., Ichimura, Y., Ohsumi, Y., Elazar, Z. EMBO Rep. (2006) [Pubmed]
  13. Starvation-induced expression of autophagy-related genes in Arabidopsis. Rose, T.L., Bonneau, L., Der, C., Marty-Mazars, D., Marty, F. Biol. Cell (2006) [Pubmed]
  14. ATG23, a novel gene required for maturation of proaminopeptidase I, but not for autophagy. Meiling-Wesse, K., Bratsika, F., Thumm, M. FEMS Yeast Res. (2004) [Pubmed]
  15. Crystallization and preliminary X-ray analysis of Atg3. Yamada, Y., Suzuki, N.N., Fujioka, Y., Ichimura, Y., Ohsumi, Y., Inagaki, F. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
  16. The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways. Huang, W.P., Scott, S.V., Kim, J., Klionsky, D.J. J. Biol. Chem. (2000) [Pubmed]
  17. Dictyostelium macroautophagy mutants vary in the severity of their developmental defects. Otto, G.P., Wu, M.Y., Kazgan, N., Anderson, O.R., Kessin, R.H. J. Biol. Chem. (2004) [Pubmed]
  18. Autophagic nutrient recycling in Arabidopsis directed by the ATG8 and ATG12 conjugation pathways. Thompson, A.R., Doelling, J.H., Suttangkakul, A., Vierstra, R.D. Plant Physiol. (2005) [Pubmed]
  19. Arabidopsis homologues of the autophagy protein Atg8 are a novel family of microtubule binding proteins. Ketelaar, T., Voss, C., Dimmock, S.A., Thumm, M., Hussey, P.J. FEBS Lett. (2004) [Pubmed]
  20. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. Kirisako, T., Baba, M., Ishihara, N., Miyazawa, K., Ohsumi, M., Yoshimori, T., Noda, T., Ohsumi, Y. J. Cell Biol. (1999) [Pubmed]
  21. Atg21 is required for effective recruitment of Atg8 to the preautophagosomal structure during the Cvt pathway. Meiling-Wesse, K., Barth, H., Voss, C., Eskelinen, E.L., Epple, U.D., Thumm, M. J. Biol. Chem. (2004) [Pubmed]
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