Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex
Open accessAbstract
Beclin 1, a mammalian autophagy protein that has been implicated in development, tumour suppression, neurodegeneration and cell death, exists in a complex with Vps34, the class III phosphatidylinositol-3-kinase (PI(3)K) that mediates multiple vesicle-trafficking processes including endocytosis and autophagy. However, the precise role of the Beclin 1-Vps34 complex in autophagy regulation remains to be elucidated. Combining mouse genetics and biochemistry, we have identified a large in vivo Beclin 1 complex containing the known proteins Vps34, p150/Vps15 and UVRAG, as well as two newly identified proteins, Atg14L (yeast Atg14-like) and Rubicon (RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein). Characterization of the new proteins revealed that Atg14L enhances Vps34 lipid kinase activity and upregulates autophagy, whereas Rubicon reduces Vps34 activity and downregulates autophagy. We show that Beclin 1 and Atg14L synergistically promote the formation of double-membraned organelles that are associated with Atg5 and Atg12, whereas forced expression of Rubicon results in aberrant late endosomal/lysosomal structures and impaired autophagosome maturation. We hypothesize that by forming distinct protein complexes, Beclin 1 and its binding proteins orchestrate the precise function of the class III PI(3)K in regulating autophagy at multiple steps.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Yeast Atg14 is the autophagy-specific subunit of the Vps34 complex I, and a human homolog named ATG14 (ATG14L/BARKOR) has been identified.
“Yeast Atg14 is the autophagy-specific subunit of the Vps34 complex I, 404 and a human homolog, named ATG14 (ATG14L/BARKOR), has been identified.[405][406][407][408]”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [406]
The passage describing protein identification (section labeled Abstract; page unavailable) reports a newly identified mammalian protein with modest similarity to yeast Atg14 and names it Atg14L. However, the protein was isolated from mouse tissues, and our copy does not identify it as a human homolog or use the name BARKOR. The yeast-complex point is also described in the paper, but the citation in question follows the human-homolog point. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe class III PI3K complex regulates vesicle nucleation and phagophore formation.
“the class III phosphoinositide 3-kinase (PI3K) complex regulates vesicle nucleation and phagophore formation”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
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
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347 · see citing works
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311 · see citing works
Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124 · see citing works
Self-citationYue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116 · see citing works
Self-citationA 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., et al. (2000) · Nature · doi:10.1038/35044114 · Cited by 2,064 · see citing works
LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., & Yoshimori, T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01131 · Cited by 1,394 · see citing works
Receptor downregulation and multivesicular-body sorting
Katzmann, D. J., Odorizzi, G., & Emr, S. D. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm973 · Cited by 1,201 · see citing works
Protection against Fatal Sindbis Virus Encephalitis by Beclin, a Novel Bcl-2-Interacting Protein
Liang, X. H., Kleeman, L. K., Jiang, H., Gordon, G. W., Goldman, J. E., Berry, G., Herman, B. A., & Levine, B. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8586-8596.1998 · Cited by 1,128 · see citing works
Ambra1 regulates autophagy and development of the nervous system
Fimia, G. M., Stoykova, A., Romagnoli, A., Giunta, L., Bartolomeo, S. D., Nardacci, R., Corazzari, M., Fuoco, C., Uçar, A., Schwartz, P. J., et al. (2007) · Nature · doi:10.1038/nature05925 · Cited by 1,048 · see citing works
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B., & Jung, J. U. (2006) · Nature Cell Biology · doi:10.1038/ncb1426 · Cited by 1,025 · see citing works
Kihara, A., Noda, T., Ishihara, N., & Ohsumi, Y. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.3.519 · Cited by 1,004 · see citing works
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis
Takahashi, Y., Coppola, D., Matsushita, N., Cualing, H. D., Sun, M., Sato, Y., Liang, C., Jung, J. U., Cheng, J. Q., Mul, J. J., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1634 · Cited by 928 · see citing works
Beclin–phosphatidylinositol 3‐kinase complex functions at the trans‐Golgi network
Kihara, A., Kabeya, Y., Ohsumi, Y., & Yoshimori, T. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve061 · Cited by 813 · see citing works
A lipid associated with the antiphospholipid syndrome regulates endosome structure and function
Kobayashi, T., Stang, E., Fang, K. S., de Moerloose, P., Parton, R. G., & Gruenberg, J. (1998) · Nature · doi:10.1038/32440 · Cited by 787 · see citing works
Komatsu, M., Wang, Q. J., Holstein, G. R., Friedrich, V. L., Iwata, J.-I., Kominami, E., Chait, B. T., Tanaka, K., & Yue, Z. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701311104 · Cited by 614 · see citing works
Self-citationRegulation of intracellular accumulation of mutant Huntingtin by Beclin 1
Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B., & Yuan, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600364200 · Cited by 458 · see citing works
Mechanism of Two Classes of Cancer Mutations in the Phosphoinositide 3-Kinase Catalytic Subunit
Miled, N., Yan, Y., Hon, W., Perišić, O., Zvelebil, M., Inbar, Y., Schneidman‐Duhovny, D., Wolfson, H. J., Backer, J., & Williams, R. L. (2007) · Science · doi:10.1126/science.1135394 · Cited by 410 · see citing works
Self-citationZeng, X., Overmeyer, J. H., & Maltese, W. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.02735 · Cited by 331 · see citing works
Induction of Autophagy in Axonal Dystrophy and Degeneration
Wang, Q. J., Ding, Y., Kohtz, S., Mizushima, N., Cristea, I. M., Rout, M. P., Chait, B. T., Zhong, Y., Heintz, N., & Yue, Z. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2261-06.2006 · Cited by 308 · see citing works
Self-citationA Novel Protein Complex Linking the δ2 Glutamate Receptor and Autophagy
Yue, Z., Horton, A., Bravin, M., DeJager, P. L., Selimi, F., & Heintz, N. (2002) · Neuron · doi:10.1016/s0896-6273(02)00861-9 · Cited by 306 · see citing works
Self-citationFluorescent Proteins as Proteomic Probes
Cristea, I. M., Williams, R., Chait, B. T., & Rout, M. P. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500227-mcp200 · Cited by 251 · see citing works
Self-citationStack, J. H., DeWald, D. B., Takegawa, K., & Emr, S. D. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.2.321 · Cited by 249 · see citing works
The phosphatidylinositol 3‐phosphate‐binding FYVE finger
Stenmark, H., Aasland, R., & Driscoll, P. C. (2002) · FEBS Letters · doi:10.1016/s0014-5793(01)03308-7 · Cited by 224 · see citing works
Gong, S., Yang, X. W., Li, C., & Heintz, N. (2002) · Genome Research · doi:10.1101/gr.476202 · Cited by 220 · see citing works
Self-citationPacheco, C. D., Kunkel, R., & Lieberman, A. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm100 · Cited by 219 · see citing works
Defective autophagy leads to cancer
Edinger, A. L., & Thompson, C. B. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00306-4 · Cited by 211 · see citing works
Yue, Z. (2007) · Autophagy · doi:10.4161/auto.3602 · Cited by 130 · see citing works
Self-citationhVps15, but not Ca2+/CaM, is required for the activity and regulation of hVps34 in mammalian cells
Yan, Y., Flinn, R. J., Wu, H., Schnur, R. S., & Backer, J. (2008) · Biochemical Journal · doi:10.1042/bj20081865 · Cited by 113 · see citing works
Self-citationProtein degradation in 3T3 cells and tumorigenic transformed 3T3 cells
Gronostajski, R. M., & Pardee, A. B. (1984) · Journal of Cellular Physiology · doi:10.1002/jcp.1041190120 · Cited by 53 · see citing works
Arsov, I., Li, X., Matthews, G., Coradin, J. H., Hartmann, B., Simon, A. K., Sealfon, S. C., & Yue, Z. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.59 · Cited by 52 · see citing works
Self-citationTeclemariam‐Mesbah, R., Wortel, J., Romijn, H. J., & Buijs, R. M. (1997) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549704500414 · Cited by 29 · see citing works
Flagged first, then by citations
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-citationCillà, S. D., Farruggio, S., Vujosevic, S., Raina, G., Filippini, D. A., Gatti, V., Clemente, N., Mary, D., Vezzola, D., Casini, G., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479441 · Cited by 5,154 · see citing works
Guidelines 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
Autophagy: cellular and molecular mechanisms
Glick, D. R., Barth, S., & Macleod, K. F. (2010) · The Journal of Pathology · doi:10.1002/path.2697 · Cited by 3,815 · see citing works
The Role of Atg Proteins in Autophagosome Formation
Mizushima, N., Yoshimori, T., & Ohsumi, Y. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154005 · Cited by 2,978 · 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
Self-citationAn 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 Beclin 1 network regulates autophagy and apoptosis
Kang, R., Zeh, H. J., Lotze, M. T., & Tang, D. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2010.191 · Cited by 2,485 · see citing works
Jung, C. H., Ro, S.-H., Cao, J., Otto, N. M., & Kim, D.-H. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.017 · Cited by 2,090 · see citing works
Mammalian autophagy: core molecular machinery and signaling regulation
Yang, Z., & Klionsky, D. J. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.11.014 · Cited by 1,956 · see citing works
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcı́a-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,726 · see citing works
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646 · see citing works
Self-citationPhosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638 · see citing works
Autophagy and autophagy-related proteins in cancer
Li, X., He, S., & Ma, B. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1138-4 · Cited by 1,653 · see citing works
Self-citationThe emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767 · see citing works
Network organization of the human autophagy system
Behrends, C., Sowa, M. E., Gygi, S. P., & Harper, J. W. (2010) · Nature · doi:10.1038/nature09204 · Cited by 1,554 · see citing works
ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y.-Y., Kim, J., Kim, H., Neufeld, T. P., Dillin, A. G., & Guan, K. (2013) · Nature Cell Biology · doi:10.1038/ncb2757 · Cited by 1,586 · see citing works
Autophagy modulation as a potential therapeutic target for diverse diseases
Rubinsztein, D. C., Codogno, P., & Levine, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3802 · Cited by 1,429 · see citing works
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · see citing works
Architecture of the human interactome defines protein communities and disease networks
Huttlin, E. L., Bruckner, R. J., Paulo, J. A., Cannon, J. R., Ting, L., Baltier, K., Colby, G., Gebreab, F., Gygi, M. P., Parzen, H., et al. (2017) · Nature · doi:10.1038/nature22366 · Cited by 1,437 · see citing works
Autophagy and autophagy-related pathways in cancer
Debnath, J., Gammoh, N., & Ryan, K. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00585-z · Cited by 1,443 · see citing works
Wu, Y.-T., Tan, H.-L., Shui, G., Bauvy, C., Huang, Q., Wenk, M. R., Ong, C.-N., Codogno, P., & Shen, H.-M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.080796 · Cited by 1,127 · see citing works
Historical landmarks of autophagy research
Ohsumi, Y. (2013) · Cell Research · doi:10.1038/cr.2013.169 · Cited by 1,093 · see citing works
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways
Palmieri, M., Impey, S., Kang, H., di Ronza, A., Pelz, C., Sardiello, M., & Ballabio, A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr306 · Cited by 1,022 · see citing works
Autophagy gone awry in neurodegenerative diseases
Wong, E. S. P., & Cuervo, A. M. (2010) · Nature Neuroscience · doi:10.1038/nn.2575 · Cited by 883 · see citing works
Mechanisms governing autophagosome biogenesis
Nakatogawa, H. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0241-0 · Cited by 876 · see citing works
Autophagy, Immunity, and Microbial Adaptations
Deretic, V. P., & Levine, B. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.05.016 · Cited by 868 · see citing works
Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13
Liu, J., Xia, H., Kim, M., Xu, L., Li, Y., Zhang, L., Cai, Y. C., Norberg, H. V., Zhang, T., Furuya, T., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.037 · Cited by 828 · see citing works
Differential Regulation of Distinct Vps34 Complexes by AMPK in Nutrient Stress and Autophagy
Kim, J., Kim, Y. C., Fang, C., Russell, R. C., Kim, J. H., Fan, W., Liu, R., Zhong, Q., & Guan, K. (2013) · Cell · doi:10.1016/j.cell.2012.12.016 · Cited by 806 · see citing works
Autophagy as a target for anticancer therapy
Jankú, F., McConkey, D. J., Hong, D. S., & Kurzrock, R. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.71 · Cited by 803 · see citing works
The Beclin 1–VPS34 complex – at the crossroads of autophagy and beyond
Funderburk, S. F., Wang, Q. J., & Yue, Z. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.03.002 · Cited by 785 · see citing works
Self-citationItakura, E., & Mizushima, N. (2010) · Autophagy · doi:10.4161/auto.6.6.12709 · Cited by 843 · see citing works
Martinez, J., Malireddi, R. K. S., Lu, Q., Cunha, L. D., Pelletier, S., Gingras, S., Orchard, R., Guan, J.-L., Tan, H., Peng, J., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3192 · Cited by 758 · see citing works
“In agreement with previous studies 14,15 , rapamycin-treated or nutrient-deprived Rubi-con macrophages exhibited increased numbers of LC3 puncta, compared with wild-type macrophages (Fig.”
RetractedAutophagy regulation by nutrient signaling
Russell, R. C., Yuan, H., & Guan, K. (2013) · Cell Research · doi:10.1038/cr.2013.166 · Cited by 713 · see citing works
Mammalian Autophagy: How Does It Work?
Bento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., Menzies, F. M., & Rubinsztein, D. C. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014556 · Cited by 692 · see citing works
Autophagy mediates degradation of nuclear lamina
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., et al. (2015) · Nature · doi:10.1038/nature15548 · Cited by 655 · see citing works
TBK-1 Promotes Autophagy-Mediated Antimicrobial Defense by Controlling Autophagosome Maturation
Pilli, M., Arko-Mensah, J., Ponpuak, M., Roberts, E., Master, S., Mandell, M. A., Dupont, N., Ornatowski, W., Jiang, S., Bradfute, S. B., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.015 · Cited by 655 · see citing works
Mechanisms of Autophagy Initiation
Hurley, J. H., & Young, L. N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044820 · Cited by 655 · see citing works
He, C., & Levine, B. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.01.001 · Cited by 659 · see citing works
Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity
Zhao, Y., Yang, J. H., Liao, W., Liu, X., Zhang, H., Wang, S., Wang, D., Feng, J., Yu, L., & Zhu, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2069 · Cited by 607 · see citing works
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes
Diao, J., Liu, R., Rong, Y., Zhao, M., Zhang, J., Lai, Y., Zhou, Q., Wilz, L., Li, J., Vivona, S., et al. (2015) · Nature · doi:10.1038/nature14147 · Cited by 592 · see citing works
The regulation of autophagy – unanswered questions
Chen, Y., & Klionsky, D. J. (2010) · Journal of Cell Science · doi:10.1242/jcs.064576 · Cited by 590 · see citing works
Machinery, regulation and pathophysiological implications of autophagosome maturation
Zhao, Y. G., Codogno, P., & Zhang, H. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00392-4 · Cited by 574 · see citing works
PLEKHM1 Regulates Autophagosome-Lysosome Fusion through HOPS Complex and LC3/GABARAP Proteins
McEwan, D. G., Popovic, D., Gubaš, A., Terawaki, S., SUZUKI, H., Stadel, D., Coxon, F. P., de Stegmann, D. M., Bhogaraju, S., Maddi, K., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.11.006 · Cited by 555 · see citing works
Grumati, P., Coletto, L., Sabatelli, P., Cescon, M., Angelin, A., Bertaggia, E., Blaauw, B., Urciuolo, A., Tiepolo, T., Merlini, L., et al. (2010) · Nature Medicine · doi:10.1038/nm.2247 · Cited by 540 · see citing works
Murrow, L. M., & Debnath, J. (2012) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163918 · Cited by 526 · see citing works
Matrix Protein 2 of Influenza A Virus Blocks Autophagosome Fusion with Lysosomes
Gannagé, M., Dormann, D., Albrecht, R., Dengjel, J., Torossi, T., Rämer, P. C., Lee, M., Strowig, T., Arrey, F., Conenello, G., et al. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.09.005 · Cited by 526 · see citing works
New insights into autophagosome–lysosome fusion
Nakamura, S., & Yoshimori, T. (2017) · Journal of Cell Science · doi:10.1242/jcs.196352 · Cited by 520 · see citing works
The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy
Bartolomeo, S. D., Corazzari, M., Nazio, F., Oliverio, S., Lisi, G., Antonioli, M., Pagliarini, V., Matteoni, S., Fuoco, C., Giunta, L., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201002100 · Cited by 519 · see citing works
Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2
Maejima, Y., Kyoi, S., Zhai, P., Liu, T., Li, H., Ivessa, A., Sciarretta, S., Del Re, D. P., Zablocki, D. K., Hsu, C.-P., et al. (2013) · Nature Medicine · doi:10.1038/nm.3322 · Cited by 499 · see citing works
Autophagy in kidney homeostasis and disease
Tang, C., Livingston, M. J., Liu, Z., & Dong, Z. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-0309-2 · Cited by 496 · see citing works
Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes
Simonsen, A., & Tooze, S. A. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200907014 · Cited by 498 · see citing works
Autophagosome Formation and Molecular Mechanism of Autophagy
Tanida, I. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3482 · Cited by 489 · see citing works
Overview of macroautophagy regulation in mammalian cells
Mehrpour, M., Esclatine, A., Beau, I., & Codogno, P. (2010) · Cell Research · doi:10.1038/cr.2010.82 · Cited by 488 · see citing works
Luciani, A., Villella, V. R., Esposito, S., Brunetti-Pierri, N., Medina, D., Settembre, C., Gavina, M., Pulze, L., Giardino, I., Pettoello-Mantovani, M., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2090 · Cited by 467 · 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
Virgin, H. W., & Levine, B. (2009) · Nature Immunology · doi:10.1038/ni.1726 · Cited by 453 · see citing works
MAPK/JNK signalling: a potential autophagy regulation pathway
Zhou, Y.-Y., Li, Y., Jiang, W.-Q., & Zhou, L.-F. (2015) · Bioscience Reports · doi:10.1042/bsr20140141 · Cited by 444 · see citing works
Ge, L., Melville, D., Zhang, M., & Schekman, R. W. (2013) · eLife · doi:10.7554/elife.00947 · Cited by 440 · see citing works
Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L
Matsunaga, K., Morita, E., Saitoh, T., Akira, S., Ktistakis, N. T., Izumi, T., Noda, T., & Yoshimori, T. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911141 · Cited by 456 · see citing works
Functions of autophagy in normal and diseased liver
Czaja, M. J., Ding, W., Donohue, T. M., Friedman, S. L., Js, K., Komatsu, M., Lemasters, J. J., Lemoine, A., Lin, J. D., Ou, J. J., et al. (2013) · Autophagy · doi:10.4161/auto.25063 · Cited by 435 · see citing works
Autophagy in osteoblasts is involved in mineralization and bone homeostasis
Nollet, M., Santucci-Darmanin, S., Breuil, V., Al-Sahlanee, R., Cros, C., Topi, M., Momier, D., Samson, M., Pagnotta, S., Cailleteau, L., et al. (2014) · Autophagy · doi:10.4161/auto.36182 · Cited by 422 · see citing works
Autophagy in lysosomal storage disorders
Lieberman, A. P., Puertollano, R., Raben, N., Slaugenhaupt, S., Walkley, S. U., & Ballabio, A. (2012) · Autophagy · doi:10.4161/auto.19469 · Cited by 399 · see citing works
Villella, V. R., Esposito, S., Bruscia, E. M., Maiuri, M. C., Raia, V., Kroemer, G., & Maiuri, L. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00001 · Cited by 389 · see citing works
Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function
Jaber, N. L., Dou, Z., Chen, J., Catanzaro, J. M., Jiang, Y.-P., Ballou, L. M., Selinger, E. S., Ouyang, X., Lin, R. Z., Zhang, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112848109 · Cited by 386 · see citing works
Tanaka, S., Hikita, H., Tatsumi, T., Sakamori, R., Nozaki, Y., Sakane, S., Shiode, Y., Nakabori, T., Saito, Y., Hiramatsu, N., et al. (2016) · Hepatology · doi:10.1002/hep.28820 · Cited by 376 · see citing works
Distinct Autophagosomal-Lysosomal Fusion Mechanism Revealed by Thapsigargin-Induced Autophagy Arrest
Ganley, I. G., Wong, P., Gammoh, N., & Jiang, X. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.024 · Cited by 382 · see citing works
Beclin-1-Dependent Autophagy Protects the Heart During Sepsis
Sun, Y., Yao, X., Zhang, Q.-J., Zhu, M., Liu, Z.-P., Ci, B., Xie, Y., Carlson, D., Rothermel, B. A., Sun, Y., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.032821 · Cited by 378 · see citing works
Autophagosome maturation: An epic journey from the ER to lysosomes
Zhao, Y. G., & Zhang, H. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201810099 · Cited by 362 · see citing works
Sarkar, S. (2013) · Biochemical Society Transactions · doi:10.1042/bst20130134 · Cited by 367 · see citing works
A current perspective of autophagosome biogenesis
Shibutani, S., & Yoshimori, T. (2013) · Cell Research · doi:10.1038/cr.2013.159 · Cited by 361 · see citing works
Park, J.-M., Jung, C. H., Seo, M., Otto, N. M., Grunwald, D., Kim, K. H., Moriarity, B., Kim, Y.-M., Starker, C., Nho, R. S., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1140293 · Cited by 341 · see citing works
Liang, Q., Seo, G. J., Choi, Y. J., Kwak, M., Ge, J., Rodgers, M. A., Shi, M., Leslie, B. J., Hopfner, K., Ha, T., et al. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.01.009 · Cited by 351 · see citing works
Gene Copy-Number Alterations: A Cost-Benefit Analysis
Tang, Y.-C., & Amon, A. (2013) · Cell · doi:10.1016/j.cell.2012.11.043 · Cited by 348 · see citing works
Starr, T., Child, R., Wehrly, T. D., Hansen, B. T., Hwang, S., López-Otı́n, C., Virgin, H. W., & Celli, J. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2011.12.002 · Cited by 341 · see citing works
LC3-Associated Phagocytosis in Myeloid Cells Promotes Tumor Immune Tolerance
Cunha, L. D., Yang, M., Carter, R., Guy, C., Harris, L., Crawford, J. C., Quarato, G., Boada-Romero, E., Kalkavan, H., Johnson, M. D. L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.061 · Cited by 334 · see citing works
Hale, A. N., Ledbetter, D., Gawriluk, T. R., & Rucker, E. B. (2013) · Autophagy · doi:10.4161/auto.24273 · Cited by 336 · see citing works
Beclin 1 Phosphorylation – at the Center of Autophagy Regulation
Menon, M., & Dhamija, S. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00137 · Cited by 342 · see citing works
Lim, J., Lachenmayer, M. L., Wu, S., Liu, W., Kundu, M., Wang, R., Komatsu, M., Oh, Y. J., Zhao, Y., & Yue, Z. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004987 · Cited by 323 · see citing works
Self-citationAutophagy and the Immune System
Kuballa, P., Nolte, W. M., Castoreno, A. B., & Xavier, R. J. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074948 · Cited by 328 · see citing works
Stavoe, A. K. H., & Holzbaur, E. L. F. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125242 · Cited by 328 · see citing works
Bodemann, B. O., Orvedahl, A., Cheng, T., Ram, R. R., Ou, Y.-H., Formstecher, É., Maiti, M., Hazelett, C. C., Wauson, E., Balakireva, M., et al. (2011) · Cell · doi:10.1016/j.cell.2010.12.018 · Cited by 317 · see citing works
The clearance of dying cells: table for two
Green, D. R., Oguin, T. H., & Martinez, J. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.172 · Cited by 314 · see citing works
Ponpuak, M., Davis, A. S., Roberts, E. A., Delgado, M. A., Dinkins, C., Zhao, Z., Virgin, H. W., Kyei, G. B., Johansen, T., Vergne, I., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.02.009 · Cited by 308 · see citing works
Why should autophagic flux be assessed?
Zhang, X.-J., Chen, S., Huang, K.-X., & Le, W.-D. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.184 · Cited by 304 · see citing works
Autophagy in diabetic nephropathy
Ding, Y., & Choi, M. E. (2015) · Journal of Endocrinology · doi:10.1530/joe-14-0437 · Cited by 306 · see citing works
The multiple roles of autophagy in cancer
Rosenfeldt, M. T., & Ryan, K. M. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr031 · Cited by 302 · see citing works
A comprehensive glossary of autophagy-related molecules and processes (2ndedition)
Klionsky, D. J., Baehrecke, E. H., Brumell, J. H., Chu, C. T., Codogno, P., Cuervo, A. M., Debnath, J., Deretic, V. P., Elazar, Z., Eskelinen, E., et al. (2011) · Autophagy · doi:10.4161/auto.7.11.17661 · Cited by 293 · see citing works
Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy
Yuan, H., Russell, R. C., & Guan, K. (2013) · Autophagy · doi:10.4161/auto.26058 · Cited by 292 · see citing works
Coronavirus NSP6 restricts autophagosome expansion
Cottam, E. M., Whelband, M., & Wileman, T. E. (2014) · Autophagy · doi:10.4161/auto.29309 · Cited by 291 · see citing works
The Role of Lipids in the Control of Autophagy
Dall’Armi, C., Devereaux, K. A., & Paolo, G. D. (2013) · Current Biology · doi:10.1016/j.cub.2012.10.041 · Cited by 286 · see citing works
Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L)
Fan, W., Nassiri, A., & Zhong, Q. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016472108 · Cited by 285 · see citing works
Kudchodkar, S. B., & Levine, B. (2009) · Reviews in Medical Virology · doi:10.1002/rmv.630 · Cited by 278 · see citing works
Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer
Bruntz, R. C., Lindsley, C. W., & Brown, H. A. (2014) · Pharmacological Reviews · doi:10.1124/pr.114.009217 · Cited by 275 · see citing works
Autophagosome formation—The role of ULK1 and Beclin1–PI3KC3 complexes in setting the stage
Wirth, M., Joachim, J., & Tooze, S. A. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.007 · Cited by 276 · see citing works
mTORC1 Phosphorylates UVRAG to Negatively Regulate Autophagosome and Endosome Maturation
Kim, Y. M., Jung, C. H., Seo, M., Kim, E. K., Park, J.-M., Bae, S. S., & Kim, D. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.11.013 · Cited by 275 · see citing works
Control of autophagy initiation by phosphoinositide 3‐phosphatase jumpy
Vergne, I., Roberts, E., Elmaoued, R. A., Tosch, V., Delgado, M. A., Proikas‐Cezanne, T., Laporte, J., & Deretic, V. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.159 · Cited by 270 · see citing works
LC3-Associated Phagocytosis and Inflammation
Heckmann, B. L., Boada-Romero, E., Cunha, L. D., Magne, J., & Green, D. R. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.08.012 · Cited by 276 · 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
LC3-associated phagocytosis at a glance
Heckmann, B. L., & Green, D. R. (2019) · Journal of Cell Science · doi:10.1242/jcs.222984 · Cited by 272 · see citing works
- Authors
- Zhong, Y., Wang, Q. J., Li, X., Yan, Y., Backer, J. M., Chait, B. T., Heintz, N., & Yue, Z.
- Affiliations
- Howard Hughes Medical Institute (US)
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Yue, Zhenyu
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2009-03-08
- Volume
- 11
- Issue
- 4
- Pages
- 468-476
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC2664389
- OpenAlex
- W1983831622
- Cited by
- 1,005
- References
- 35
- Citations by year
- 2026: 29 · 2025: 43 · 2024: 38 · 2023: 48 · 2022: 63 · 2021: 62 · 2020: 69 · 2019: 51 · 2018: 57 · 2017: 58 · 2016: 72 · 2015: 56 · 2014: 64 · 2013: 77 · 2012: 64
- FWCI
- 49.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (RNS055683A)
- National Institute of Neurological Disorders and Stroke (R21NS055683, R01NS060123)
- National Center for Research Resources (RR00862, P41RR000862, RR 022220, U54RR022220)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy regulation, Beclin-1, ATG14L, Rubicon, Vps34, class III phosphatidylinositol 3-kinase, UVRAG, autophagosome maturation, late endosomes, lysosomes, ATG5, ATG12, lipid kinase activity
- MeSH terms
- Beclin-1, Amino Acid Sequence, Animals, Autophagy, Cell Membrane, HeLa Cells, Humans, Lysosomes, Molecular Sequence Data, Protein Binding, Proteins, Endosomes, Phosphatidylinositol Phosphates, Phosphatidylinositol 3-Kinases, NIH 3T3 Cells, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Apoptosis Regulatory Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
