LC3 and GATE‐16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis
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Autophagy, a critical process for bulk degradation of proteins and organelles, requires conjugation of Atg8 proteins to phosphatidylethanolamine on the autophagic membrane. At least eight different Atg8 orthologs belonging to two subfamilies (LC3 and GATE-16/GABARAP) occur in mammalian cells, but their individual roles and modes of action are largely unknown. In this study, we dissect the activity of each subfamily and show that both are indispensable for the autophagic process in mammalian cells. We further show that both subfamilies act differently at early stages of autophagosome biogenesis. Accordingly, our results indicate that LC3s are involved in elongation of the phagophore membrane whereas the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation.
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Recent work indicates the two LC3 subfamilies act differently at early stages of autophagosome biogenesis: the LC3 subfamily is required for elongation of the phagophore membrane, whereas the GABARAP/GATE subfamily is required for a later stage in autophagosome maturation.
“Recent work has indicated that the two subfamilies act differently at early stages of autophagosome biogenesis. Thus, the LC3 subfamily is required for elongation of the phagophore membrane, whereas the GABARAP/GATE subfamily is required for a later stage in autophagosome maturation [32]”
From LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy (2012) · cites this paper as [32]
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Cites
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · see citing works
Self-citationNix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
The Atg12-Atg5 Conjugate Has a Novel E3-like Activity for Protein Lipidation in Autophagy
Hanada, T., Noda, N. N., Satomi, Y., Ichimura, Y., Fujioka, Y., Takao, T., Inagaki, F., & Ohsumi, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700195200 · Cited by 1,123 · cited 2× · see citing works
“Moreover, the Atg12–Atg5 conjugate may act as an E3-like enzyme for the conjugation of Atg8s to PE and, together with Atg16, is responsible for their recruit- ment to the phagophore (Hanada et al, 2007; Fujita et al, 2008b).”
BackgroundMizushima, N., Kuma, A., Kobayashi, Y., Yamamoto, A., Matsubae, M., Takao, T., Natsume, T., Ohsumi, Y., & Yoshimori, T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00381 · Cited by 791 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Geng J, Klionsky DJ (2008) The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 0 Protein modifications: beyond the usual suspects 0 review series. EMBO Rep 9: 859-864
- Orci L, Tagaya M, Amherdt M, Perrelet A, Donaldson JG, Lippincott- Schwartz J, Klausner RD, Rothman JE (1991) Brefeldin A, a drug that blocks secretion, prevents the assembly of non-clathrin- coated buds on Golgi cisternae. Cell 64: 1183-1195
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · see citing works
Self-citationAutophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506 · see citing works
Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289 · see citing works
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
An Overview of Autophagy: Morphology, Mechanism, and Regulation
Parzych, K. R., & Klionsky, D. J. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5371 · Cited by 2,521 · see citing works
The machinery of macroautophagy
Feng, Y., He, D., Yao, Z., & Klionsky, D. J. (2014) · Cell Research · doi:10.1038/cr.2013.168 · Cited by 2,083 · see citing works
Regulation of autophagy by ROS: physiology and pathology
Scherz-Shouval, R., & Elazar, Z. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.007 · Cited by 1,263 · see citing works
Self-citationCargo recognition and trafficking in selective autophagy
Stolz, A., Ernst, A., & Dikic, I. (2014) · Nature Cell Biology · doi:10.1038/ncb2979 · Cited by 1,207 · see citing works
Rogov, V., Dötsch, V., Johansen, T., & Kirkin, V. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.014 · Cited by 992 · see citing works
Ubiquitination and selective autophagy
Shaid, S., Brandts, C. H., Serve, H., & Dikic, I. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.72 · Cited by 800 · see citing works
Atg8: an autophagy-related ubiquitin-like protein family.
Shpilka, T., Weidberg, H., Pietrokovski, S., & Elazar, Z. (2011) · Genome biology · doi:10.1186/gb-2011-12-7-226 · Cited by 543 · see citing works
“Apparently, both the LC3 and the GABARAP/GATE-16 subfamilies are essential for autophagy, as they act at different stages of autophagosome formation: members of the LC3 subfamily are responsible for the elongation of the autophagic membrane, whereas GABARAP/GATE-16 subfamily members act downstream in a step coupled to…”
BackgroundAutophagy Proteins Regulate the Secretory Component of Osteoclastic Bone Resorption
DeSelm, C. J., Miller, B. C., Zou, W., Beatty, W. L., van Meel, E., Takahata, Y., Klumperman, J., Tooze, S. A., Teitelbaum, S. L., & Virgin, H. W. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.08.016 · Cited by 487 · see citing works
Florey, O., Kim, S. E., Sandoval, C. P., Haynes, C. M., & Overholtzer, M. (2011) · Nature Cell Biology · doi:10.1038/ncb2363 · Cited by 459 · see citing works
Biogenesis and Cargo Selectivity of Autophagosomes
Weidberg, H., Shvets, E., & Elazar, Z. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052709-094552 · Cited by 466 · see citing works
Self-citationLőrincz, P., & Juhász, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.028 · Cited by 328 · see citing works
Molecular Mechanisms of Autophagy in the Cardiovascular System
Gatica, D., Chiong, M., Lavandero, S., & Klionsky, D. J. (2015) · Circulation Research · doi:10.1161/circresaha.114.303788 · Cited by 272 · see citing works
Autophagy and Its Normal and Pathogenic States in the Brain
Yamamoto, A., & Yue, Z. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014149 · Cited by 204 · see citing works
Endocytosis and Autophagy: Exploitation or Cooperation?
Tooze, S. A., Abada, A., & Elazar, Z. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018358 · Cited by 202 · see citing works
Self-citationCharacterization of macroautophagic flux in vivo using a leupeptin-based assay
Haspel, J., Shaik, R. S., Ifedigbo, E., Nakahira, K., Dolinay, T., Englert, J. A., & Choi, A. M. K. (2011) · Autophagy · doi:10.4161/auto.7.6.15100 · Cited by 152 · see citing works
LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy
Lai, S.-C., & Devenish, R. J. (2012) · Cells · doi:10.3390/cells1030396 · Cited by 116 · see citing works
Reactivation of autophagy by spermidine ameliorates the myopathic defects of collagen VI-null mice
Chrisam, M., Pirozzi, M., Castagnaro, S., Blaauw, B., Polishchuck, R., Cecconi, F., Grumati, P., & Bonaldo, P. (2015) · Autophagy · doi:10.1080/15548627.2015.1108508 · Cited by 101 · see citing works
Kumar, S., Jain, A., Choi, S. W., da Silva, G. P. D., Allers, L., Mudd, M. H., Peters, R. S., Anonsen, J. H., Rusten, T.-E., Lazarou, M., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0549-1 · Cited by 95 · see citing works
Satyavarapu, E. M., Das, R., Mandal, C., Mukhopadhyay, A., & Mandal, C. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0989-8 · Cited by 69 · see citing works
RetractedThe lifecycle of skeletal muscle mitochondria in obesity
Pileggi, C. A., Parmar, G., & Harper, M. (2021) · Obesity Reviews · doi:10.1111/obr.13164 · Cited by 61 · see citing works
Murase, D., Kusaka-Kikushima, A., Hachiya, A., Fullenkamp, R., Stepp, A., Imai, A., Ueno, M., Kawabata, K., Takahashi, Y., Hase, T., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165708 · Cited by 52 · see citing works
LC3B is indispensable for selective autophagy of p62 but not basal autophagy.
Maruyama, Y., Sou, Y.-S., Kageyama, S., Takahashi, T., Ueno, T., Tanaka, K., Komatsu, M., & Ichimura, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.093 · Cited by 56 · see citing works
Autophagy proteins regulate cell engulfment mechanisms that participate in cancer
Kim, S. E., & Overholtzer, M. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.004 · Cited by 35 · see citing works
- Authors
- Weidberg, H., Shvets, E., Shpilka, T., Shimron, F., Shinder, V., & Elazar, Z.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Elazar, Zvulun
- Venue
- The EMBO Journal
- Published
- 2010-04-23
- Volume
- 29
- Issue
- 11
- Pages
- 1792-1802
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2885923
- OpenAlex
- W2073963703
- Cited by
- 777
- References
- 5
- Citations by year
- 2026: 21 · 2025: 33 · 2024: 63 · 2023: 53 · 2022: 44 · 2021: 45 · 2020: 60 · 2019: 64 · 2018: 49 · 2017: 48 · 2016: 53 · 2015: 51 · 2014: 58 · 2013: 33 · 2012: 60
- FWCI
- 31.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Weizmann Institute of Science
- Israel Science Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › 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, autophagosome formation, LC3, GABARAP, ATG8, phosphatidylethanolamine conjugation, autophagosome maturation, mammalian cells
- MeSH terms
- Autophagy, Humans, Lysosomes, Phosphatidylethanolamines, Proteins
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