ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery
Open accessAbstract
Autophagy, the starvation-induced degradation of bulky cytosolic components, is up-regulated in mammalian cells when nutrient supplies are limited. Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates autophagy has remained elusive. Here, we identify that mTOR phosphorylates a mammalian homologue of Atg13 and the mammalian Atg1 homologues ULK1 and ULK2. The mammalian Atg13 binds both ULK1 and ULK2 and mediates the interaction of the ULK proteins with FIP200. The binding of Atg13 stabilizes and activates ULK and facilitates the phosphorylation of FIP200 by ULK, whereas knockdown of Atg13 inhibits autophagosome formation. Inhibition of mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and activates ULK to phosphorylate FIP200. These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling.
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?
Initiation of autophagosome formation begins with dissociation of MTOR from the phagophore assembly site, cued by nutrient starvation or treatment with rapamycin or its derivatives.
“The initiation step begins with the dissociation of MTOR (mechanistic target of rapamycin kinase) from the PAS, cued by nutrient starvation or treatment with rapamycin or its various derivatives [36,37].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [36]
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
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · 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
Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 2,974 · see citing works
Self-citationHow to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · cited 5× · see citing works
“The lentiviral shRNA-transduced cells or MEF cells were treated with rapamycin or vehicle for 4 h in the presence or absence of pepstatin A (10 g/ml) and E-64 (10 g/ml).”
BackgroundMethodInfluentialRavikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · 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
Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., & Deretic, V. (2004) · Cell · doi:10.1016/j.cell.2004.11.038 · Cited by 2,252 · see citing works
Yue, 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
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076 · see citing works
TOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914 · 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
Tor, a Phosphatidylinositol Kinase Homologue, Controls Autophagy in Yeast
Noda, T., & Ohsumi, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.7.3963 · Cited by 1,308 · see citing works
Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in <i>C. elegans</i>
Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.-L., Hall, D. H., & Levine, B. (2003) · Science · doi:10.1126/science.1087782 · Cited by 1,270 · see citing works
Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,211 · see citing works
Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40
Haar, E. V., Lee, S.-I., Bandhakavi, S., Griffin, T. J., & Kim, D. (2007) · Nature Cell Biology · doi:10.1038/ncb1547 · Cited by 1,185 · see citing works
Self-citationTor-Mediated Induction of Autophagy via an Apg1 Protein Kinase Complex
Kamada, Y., Funakoshi, T., Shintani, T., Nagano, K., Ohsumi, M., & Ohsumi, Y. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.150.6.1507 · Cited by 1,145 · see citing works
FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells
Hara, T., Takamura, A., Kishi, C., Iemura, S.-I., Natsume, T., Guan, J., & Mizushima, N. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200712064 · Cited by 971 · see citing works
Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body
Scott, R. C., Schuldiner, O., & Neufeld, T. P. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.07.009 · Cited by 963 · see citing works
Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
Zhang, Y., Gao, X., Saucedo, L. J., Ru, B., Edgar, B. A., & Pan, D. (2003) · Nature Cell Biology · doi:10.1038/ncb999 · Cited by 924 · see citing works
Direct Induction of Autophagy by Atg1 Inhibits Cell Growth and Induces Apoptotic Cell Death
Scott, R. C., Juhász, G., & Neufeld, T. P. (2007) · Current Biology · doi:10.1016/j.cub.2006.10.053 · Cited by 851 · see citing works
Escape of Intracellular Shigella from Autophagy
Ogawa, M., Yoshimori, T., Suzuki, T., Sagara, H., Mizushima, N., & Sasakawa, C. (2004) · Science · doi:10.1126/science.1106036 · Cited by 830 · see citing works
Hierarchy of Atg proteins in pre‐autophagosomal structure organization
Suzuki, K., Kubota, Y., Sekito, T., & Ohsumi, Y. (2007) · Genes to Cells · doi:10.1111/j.1365-2443.2007.01050.x · Cited by 691 · see citing works
Rheb promotes cell growth as a component of the insulin/TOR signalling network
Saucedo, L. J., Gao, X., Chiarelli, D. A., Li, L., Pan, D., & Edgar, B. A. (2003) · Nature Cell Biology · doi:10.1038/ncb996 · Cited by 658 · see citing works
Autophagy Is Essential for Preimplantation Development of Mouse Embryos
Tsukamoto, S., Kuma, A., Murakami, M., Kishi, C., Yamamoto, A., & Mizushima, N. (2008) · Science · doi:10.1126/science.1154822 · Cited by 618 · see citing works
Kundu, M., Lindsten, T., Yang, C.-Y., Wu, J., Zhao, F., Zhang, J., Selak, M. A., Ney, P. A., & Thompson, C. B. (2008) · Blood · doi:10.1182/blood-2008-02-137398 · Cited by 571 · see citing works
Self-citationRheb is an essential regulator of S6K in controlling cell growth in Drosophila
Stocker, H., Radimerski, T., Schindelholz, B., Wittwer, F., Belawat, P., Daram, P., Breuer, S., Thomas, G., & Hafen, E. (2003) · Nature Cell Biology · doi:10.1038/ncb995 · Cited by 530 · see citing works
Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae
Matsuura, A., Tsukada, M., Wada, Y., & Ohsumi, Y. (1997) · Gene · doi:10.1016/s0378-1119(97)00084-x · Cited by 489 · see citing works
siRNA Screening of the Kinome Identifies ULK1 as a Multidomain Modulator of Autophagy
Chan, E. Y. W., Kır, S., & Tooze, S. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703663200 · Cited by 468 · see citing works
Vacuolar Import of Proteins and Organelles From The Cytoplasm
Klionsky, D. J., & Ohsumi, Y. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.1 · Cited by 467 · see citing works
Chan, E. Y. W., Longatti, A., McKnight, N. C., & Tooze, S. A. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01082-08 · Cited by 435 · see citing works
An Atg1/Atg13 Complex with Multiple Roles in TOR-mediated Autophagy Regulation
Chang, Y.-Y., & Neufeld, T. P. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1250 · Cited by 418 · see citing works
Meijer, W. H., van der Klei, I. J., Marten Veenhuis, A., & Kiel, J. A. K. W. (2007) · Autophagy · doi:10.4161/auto.3595 · Cited by 261 · see citing works
Atg17 Regulates the Magnitude of the Autophagic Response
Cheong, H., Yorimitsu, T., Reggiori, F., Legakis, J. E., Wang, C.-W., & Klionsky, D. J. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-10-0894 · Cited by 210 · see citing works
Role of Unc51.1 and its binding partners in CNS axon outgrowthPreprint
Tomoda, T., Kim, J. H., Zhan, C., & Hatten, M. E. (2004) · Genes & Development · doi:10.1101/gad.1151204 · Cited by 191 · see citing works
Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae
Funakoshi, T., Matsuura, A., Noda, T., & Ohsumi, Y. (1997) · Gene · doi:10.1016/s0378-1119(97)00031-0 · Cited by 166 · see citing works
ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase
Lee, S. B., Kim, S., Lee, J., Park, J., Lee, G., Kim, Y., Kim, J., & Chung, J. (2007) · EMBO Reports · doi:10.1038/sj.embor.7400917 · Cited by 140 · see citing works
Self-citationDictyostelium Macroautophagy Mutants Vary in the Severity of Their Developmental Defects
Otto, G. P., Wu, M., Kazgan, N., Anderson, O. R., & Kessin, R. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311139200 · Cited by 137 · see citing works
Okazaki, N., Yan, J. C., Yuasa, S., Ueno, T., Kominami, E., Masuho, Y., Koga, H., & Muramatsu, M. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00218-7 · Cited by 128 · see citing works
Neufeld, T. P., & Baehrecke, E. H. (2008) · Autophagy · doi:10.4161/auto.5782 · Cited by 56 · see citing works
Function of theDictyostelium discoideumAtg1 Kinase during Autophagy and Development
Tekinay, T., Wu, M., Otto, G. P., Anderson, O. R., & Kessin, R. H. (2006) · Eukaryotic Cell · doi:10.1128/ec.00342-05 · Cited by 49 · see citing works
Regulation of cell growth by autophagy
Vellai, T., Bicsák, B., Tóth, M. L., Takács‐Vellai, K., & Kovács, A. L. (2008) · Autophagy · doi:10.4161/auto.5670 · Cited by 48 · see citing works
A Novel Vacuolar Myopathy with Dilated Cardiomyopathy
Sugimoto, S. (2007) · Autophagy · doi:10.4161/auto.4931 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Self-citationGuidelines 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-citationmTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941 · 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
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Self-citationMTOR: a pharmacologic target for autophagy regulation
Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126 · see citing works
Self-citationJung, 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
Self-citationThe 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
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076 · 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
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
Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks
Alers, S., Löffler, A. S., Wesselborg, S., & Stork, B. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06159-11 · Cited by 1,483 · see citing works
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
The role of the Atg1/ULK1 complex in autophagy regulation
Mizushima, N. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.004 · Cited by 1,062 · see citing works
Making new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053 · see citing works
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau
Caccamo, A., Majumder, S., Richardson, A., Strong, R., & Oddo, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100420 · Cited by 881 · see citing works
Amino acid signalling upstream of mTOR
Jewell, J. L., Russell, R. C., & Guan, K.-L. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3522 · Cited by 894 · see citing works
The mammalian ULK1 complex and autophagy initiation
Zachari, M., & Ganley, I. G. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170021 · Cited by 789 · see citing works
Martinez, J., Almendinger, J., Oberst, A., Ness, R., Dillon, C. P., Fitzgerald, P., Hengartner, M. O., & Green, D. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113421108 · Cited by 655 · see citing works
RetractedSpatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes
Narita, M., Young, A. R. J., Arakawa, S., Samarajiwa, S. A., Nakashima, T., Yoshida, S., Hong, S., Berry, L. S., Reichelt, S., Ferreira, M., et al. (2011) · Science · doi:10.1126/science.1205407 · Cited by 594 · see citing works
mTOR coordinates protein synthesis, mitochondrial activity and proliferation
Morita, M., Gravel, S.-P., Hulea, L., Larsson, O., Pollak, M., St-Pierre, J., & Topisirovic, I. (2015) · Cell Cycle · doi:10.4161/15384101.2014.991572 · Cited by 552 · see citing works
Autophagy in the liver: functions in health and disease
Ueno, T., & Komatsu, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.185 · Cited by 500 · see citing works
The Association of AMPK with ULK1 Regulates Autophagy
Lee, J. W., Park, S., Takahashi, Y., & Wang, H.-G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015394 · Cited by 482 · see citing works
Targeting ER stress–induced autophagy overcomes BRAF inhibitor resistance in melanoma
Ma, X.-H., Piao, S.-F., Dey, S., Mcafee, Q., Karakousis, G., Villanueva, J., Hart, L. S., Levi, S., Hu, J., Zhang, G., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci70454 · Cited by 457 · 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
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
Galectin-3 Coordinates a Cellular System for Lysosomal Repair and Removal
Jia, J., Claude-Taupin, A., Gu, Y., Choi, S. W., Peters, R., Bissa, B., Mudd, M. H., Allers, L., Pallikkuth, S., Lidke, K. A., et al. (2020) · Developmental Cell · doi:10.1016/j.devcel.2019.10.025 · Cited by 434 · see citing works
The Autophagy–Lysosomal Pathway in Neurodegeneration: A TFEB Perspective
Martini-Stoica, H., Xu, Y., Ballabio, A., & Zheng, H. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.02.002 · Cited by 436 · see citing works
<scp>mTOR</scp> , metabolism, and the regulation of T‐cell differentiation and function
Waickman, A. T., & Powell, J. D. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01152.x · Cited by 420 · see citing works
The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy
Webster, C. P., Smith, E. F., Bauer, C. S., Moller, A., Hautbergue, G. M., Ferraiuolo, L., Myszczynska, M. A., Higginbottom, A., Walsh, M. J., Whitworth, A. J., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201694401 · Cited by 404 · see citing works
Autophagy in acute kidney injury
Kaushal, G. P., & Shah, S. V. (2016) · Kidney International · doi:10.1016/j.kint.2015.11.021 · Cited by 389 · see citing works
Nutrient acquisition strategies of mammalian cells
Palm, W., & Thompson, C. B. (2017) · Nature · doi:10.1038/nature22379 · Cited by 388 · see citing works
Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection
Kimmey, J. M., Huynh, J. P., Weiss, L. A., Park, S., Kambal, A., Debnath, J., Virgin, H. W., & Stallings, C. L. (2015) · Nature · doi:10.1038/nature16451 · Cited by 382 · 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
Self-citationOncogenic Roles of the PI3K/AKT/mTOR axis
Aoki, M., & Fujishita, T. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_6 · Cited by 355 · see citing works
Fyfe, J. J., Bishop, D. J., & Stepto, N. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0162-1 · Cited by 347 · see citing works
TBK1: a new player in ALS linking autophagy and neuroinflammation
Oakes, J. A., Davies, M. C., & Collins, M. O. (2017) · Molecular Brain · doi:10.1186/s13041-017-0287-x · Cited by 319 · see citing works
Autophagy and neurodegeneration
Frake, R. A., Ricketts, T., Menzies, F. M., & Rubinsztein, D. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73944 · Cited by 332 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation
Tang, A. H., & Rando, T. A. (2014) · The EMBO Journal · doi:10.15252/embj.201488278 · Cited by 294 · 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
Jhanwar-Uniyal, M., Wainwright, J. V., Mohan, A. L., Tobias, M. E., Murali, R., Gandhi, C. D., & Schmidt, M. H. (2019) · Advances in Biological Regulation · doi:10.1016/j.jbior.2019.03.003 · Cited by 268 · see citing works
Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential
Yang, D., Livingston, M. J., Liu, Z., Dong, G., Zhang, M., Chen, J.-K., & Dong, Z. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2639-1 · Cited by 252 · see citing works
Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop
Löffler, A. S., Alers, S., Dieterle, A. M., Keppeler, H., Franz-Wachtel, M., Kundu, M., Campbell, D. G., Wesselborg, S., Alessi, D. R., & Stork, B. (2011) · Autophagy · doi:10.4161/auto.7.7.15451 · Cited by 258 · see citing works
Self-citationZhang, J., Kim, J., Alexander, A., Cai, S., Tripathi, D. N., Dere, R., Tee, A. R., Tait-Mulder, J., Di Nardo, A., Han, J. M., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2822 · Cited by 258 · see citing works
Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A
Wong, P.-M., Feng, Y., Wang, J., Shi, R., & Jiang, X. (2015) · Nature Communications · doi:10.1038/ncomms9048 · Cited by 239 · see citing works
Regulation of autophagy by phosphatidylinositol 3‐phosphate
Burman, C., & Ktistakis, N. T. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.011 · Cited by 234 · see citing works
Dunlop, E. A., Hunt, D. K., Acosta-Jaquez, H. A., Fingar, D. C., & Tee, A. R. (2011) · Autophagy · doi:10.4161/auto.7.7.15491 · Cited by 219 · see citing works
mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex
Chan, E. Y. (2009) · Science Signaling · doi:10.1126/scisignal.284pe51 · Cited by 214 · see citing works
Autophagy and microtubules - new story, old players
Mackeh, R., Perdiz, D., Lorin, S., Codogno, P., & Poüs, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.115626 · Cited by 212 · see citing works
Roles of mTOR complexes in the kidney: implications for renal disease and transplantation
Fantus, D., Rogers, N. M., Grahammer, F., Huber, T. B., & Thomson, A. W. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.108 · Cited by 208 · see citing works
Stressin’ Sestrins take an aging fight
Budanov, A. V., Lee, J. H., & Karin, M. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000097 · Cited by 208 · see citing works
Therapeutic targeting of autophagy in neurodegenerative and infectious diseases
Rubinsztein, D. C., Bento, C. F., & Deretic, V. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20150956 · Cited by 202 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“This complex is composed of three ULK (unc-51 like autophagy activating kinases; ULK1, ULK2, and ULK3), ATG13 (autophagy related 13), ATG101, and RB1CC1/FIP200 [36].”
Liu, R., Li, J., Zhang, T., Zou, L., Chen, Y., Wang, K., Lei, Y., Yuan, K., Li, Y., Lan, J., et al. (2014) · Autophagy · doi:10.4161/auto.28912 · Cited by 178 · see citing works
Gao, W., Shen, Z., Shang, L., & Wang, X. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2011.33 · Cited by 178 · see citing works
ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction
Park, J.-M., Seo, M., Jung, C. H., Grunwald, D., Stone, M., Otto, N. M., Toso, E., Ahn, Y., Kyba, M., Griffin, T. J., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1422851 · Cited by 168 · see citing works
Self-citationSestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals
Segalés, J., Perdiguero, E., Serrano, A. L., Sousa-Victor, P., Ortet, L., Jardí, M., Budanov, A. V., Garcia-Prat, L., Sandri, M., Thomson, D. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13832-9 · Cited by 153 · see citing works
Coordinate Autophagy and mTOR Pathway Inhibition Enhances Cell Death in Melanoma
Xie, X., White, E. P., & Mehnert, J. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055096 · Cited by 150 · see citing works
Characterization 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
Autophagy and misfolded proteins in neurodegeneration
Metcalf, D. J., García-Arencibia, M., Hochfeld, W. E., & Rubinsztein, D. C. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.003 · Cited by 138 · see citing works
Bartolomé, A., García-Aguilar, A., Asahara, S.-I., Kido, Y., Guillén, C., Pajvani, U. B., & Benito, M. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00441-17 · Cited by 141 · see citing works
Yang, F., Chu, X., Yin, M., Liu, X., Yuan, H., Niu, Y., & Fu, L. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.02.005 · Cited by 136 · see citing works
Autophagy Dysfunction in Alzheimer’s Disease: Mechanistic Insights and New Therapeutic Opportunities
Di Meco, A., Curtis, M. E., Lauretti, E., & Praticò, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.008 · Cited by 133 · see citing works
Chen, X., Wang, K., Xing, Y., Tu, J., Yang, X., Zhao, Q., Li, K., & Chen, Z. (2014) · Protein & Cell · doi:10.1007/s13238-014-0104-6 · Cited by 130 · see citing works
Tripathi, P., Rodriguez-Muela, N., Klim, J. R., de Boer, A. S., Agrawal, S., Sandoe, J., Lopes, C. S., Ogliari, K. S., Williams, L. A., Shear, M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.008 · Cited by 123 · see citing works
Yao, J., Jia, L., Khan, N., Lin, C., Mitter, S. K., Boulton, M. E., Dunaief, J. L., Klionsky, D. J., Guan, J.-L., Thompson, D. A., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1041699 · Cited by 130 · see citing works
Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts
Chiao, Y. A., Kolwicz, S. C., Basisty, N., Gagnidze, A., Zhang, J., Gu, H., Djukovic, D., Beyer, R. P., Raftery, D., MacCoss, M., et al. (2016) · Aging · doi:10.18632/aging.100881 · Cited by 128 · see citing works
Insulin Regulation of Proteostasis and Clinical Implications
James, H. A., O'Neill, B. T., & Nair, K. S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.010 · Cited by 121 · see citing works
Podocytes maintain high basal levels of autophagy independent of mtor signaling
Bork, T., Liang, W., Yamahara, K., Lee, P., Tian, Z., Liu, S., Schell, C., Thedieck, K., Hartleben, B., Patel, K., et al. (2020) · Autophagy · doi:10.1080/15548627.2019.1705007 · Cited by 100 · see citing works
Defective Autophagy and mTORC1 Signaling in Myotubularin Null Mice
Fetalvero, K. M., Yu, Y., Goetschkes, M., Liang, G., Valdez, R. A., Gould, T., Triantafellow, E., Bergling, S., Loureiro, J., Eash, J., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01075-12 · Cited by 96 · see citing works
Crosstalk between apoptosis and autophagy signaling pathways
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2020.01.003 · Cited by 92 · see citing works
SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling
Kim, Y.-M., Stone, M., Hwang, T. H., Kim, Y.-G., Dunlevy, J. R., Griffin, T. J., & Kim, D.-H. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.007 · Cited by 88 · see citing works
Self-citationMTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy
Ma, X., Zhang, S., He, L., Rong, Y., Brier, L. W., Sun, Q., Liu, R., Fan, W., Chen, S., Yue, Z., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1269988 · Cited by 92 · see citing works
The pleiotropic roles of autophagy regulators in melanogenesis
Ho, H., & Ganesan, A. K. (2011) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2011.00889.x · Cited by 88 · see citing works
Autophagy in Pulmonary Diseases
Nakahira, K., Pabon Porras, M. A., & Choi, A. M. K. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201512-2468so · Cited by 78 · see citing works
Zhao, F., Huang, W., Zhang, Z., Mao, L., Han, Y., Yan, J., & Lei, M. (2016) · Oncotarget · doi:10.18632/oncotarget.6783 · Cited by 77 · see citing works
The 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
Recent progress in the role of autophagy in neurological diseases
Meng, T., Lin, S., Zhuang, H., Huang, H., He, Z., Hu, Y., Gong, Q., & Feng, D. (2019) · Cell Stress · doi:10.15698/cst2019.05.186 · Cited by 58 · see citing works
Liu, P., Liu, K., Gu, H., Wang, W., Gong, J., Zhu, Y., Zhao, Q., Cao, J., Han, C., Gao, F., et al. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.90 · Cited by 58 · see citing works
Self-citationThe role of mitochondria in <scp>mTOR</scp>‐regulated longevity
Wei, Y., Zhang, Y., Cai, Y., & Xu, M. (2015) · Biological Reviews · doi:10.1111/brv.12103 · Cited by 56 · see citing works
Novel Insights into the Anti-Aging Role of Mitophagy
(2018) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2018.05.005 · Cited by 56 · see citing works
Sun, Y., Li, T. Y., Song, L., Zhang, C., Li, J., Lin, Z., Lin, S., & Lin, S. (2018) · Hepatology · doi:10.1002/hep.29759 · Cited by 43 · see citing works
Ost, M., Werner, F., Dokas, J., Klaus, S., & Voigt, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094689 · Cited by 27 · see citing works
Tol, M. J., van der Lienden, M. J. C., Gabriel, T. L., Hagen, J. J., Scheij, S., Veenendaal, T., Klumperman, J., Donker-Koopman, W. E., Verhoeven, A. J., Overkleeft, H., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1419118 · Cited by 27 · see citing works
Sharma, N., Singh, L., Sharma, A., Kumar, A., & Mahajan, D. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107375 · Cited by 16 · see citing works
- Authors
- Jung, C. H., Jun, C. B., Ro, S.-H., Kim, Y.-M., Otto, N. M., Cao, J., Kundu, M., & Kim, D.-H.
- Affiliations
- University of Minnesota (US)
- St. Jude Children's Research Hospital (US)
- Venue
- Molecular Biology of the Cell
- Published
- 2009-04
- Volume
- 20
- Issue
- 7
- Pages
- 1992-2003
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2663920
- OpenAlex
- W2113432343
- Cited by
- 2,025
- References
- 43
- Citations by year
- 2026: 64 · 2025: 65 · 2024: 108 · 2023: 132 · 2022: 111 · 2021: 146 · 2020: 154 · 2019: 118 · 2018: 116 · 2017: 149 · 2016: 146 · 2015: 126 · 2014: 132 · 2013: 117 · 2012: 122
- FWCI
- 76.67
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- American Diabetes Association
- American Heart Association
- Tuberous Sclerosis Alliance
- National Institutes of Health (DK072004)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072004, P30 DK 50456, P30DK050456, DK072004, R56DK072004)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- autophagy, mTOR signaling, ULK1, ULK2, ATG13, FIP200, autophagosome formation, protein phosphorylation, leucine deprivation, rapamycin, nutrient deprivation
- MeSH terms
- Autophagy-Related Proteins, Autophagy-Related Protein-1 Homolog, Animals, Autophagy, Cell Line, Humans, Phagosomes, Phosphorylation, Protein Binding, Protein Kinases, Protein-Tyrosine Kinases, Signal Transduction, Protein Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, TOR Serine-Threonine Kinases
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