Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy

Nicklin, Paul; Bergman, Philip; Zhang, Bailin; Triantafellow, Ellen; Wang, Henry; Nyfeler, Beat; Yang, Haidi; Hild, Marc; Kung, Charles; Wilson, Christopher; Myer, Vic E.; MacKeigan, Jeffrey P.; Porter, Jeffrey A.; Wang, Y. Karen; Cantley, Lewis C.; Finan, Peter M.; Murphy, Leon O.

doi:10.1016/j.cell.2008.11.044

Cited by 1,798Amino Acid Enzymes and MetabolismPI3K/AKT/mTOR signaling in cancerAutophagy in Disease and Therapy

Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy

Open access

Nicklin, Paul, Bergman, Philip, Zhang, Bailin, Triantafellow, Ellen, Wang, Henry, Nyfeler, Beat, Yang, Haidi, Hild, Marc +9 more·2009·Cell

DOI 10.1016/j.cell.2008.11.044PMC PMC3733119

Open this paper in CoChat — free account Open PDF

Abstract

Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.

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

Crossref · 10.1016/j.cell.2008.11.044

Cites

59 of 59 references verified0 citation errors · 0 not checkable

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?

Cellular uptake of glutamine and its subsequent efflux in the presence of essential amino acids is the rate-determining step for mTORC1 activation.
“It has been reported that cellular uptake of glutamine and its subsequent efflux in the presence of essential amino acids, including leucine, is the rate-determining step that activates mTORC1191.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [191]
Import of leucine through LAT1 is coupled to simultaneous efflux of glutamine.
“the import of an essential amino acid leucine through the plasma membrane-localized neutral amino acid antiporter LAT1 was shown to be coupled to a simultaneous efflux of glutamine”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Nicklin et al., 2009

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.
Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,135 · see citing works
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773 · see citing works
Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752 · see citing works
Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works
Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622 · see citing works
Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3
Kimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278 · see citing works
Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Rüegg, M. A., Hall, A., & Hall, M. N. (2004) · Nature Cell Biology · doi:10.1038/ncb1183 · Cited by 2,097 · see citing works
Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019 · see citing works
Self-citation
The Tuberous Sclerosis Complex
Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793 · see citing works
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,556 · see citing works
Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism
Hara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370 · see citing works
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349 · see citing works
Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction.
Takeshige, K., Baba, M., Tsuboi, S., Noda, T., & Ohsumi, Y. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.2.301 · Cited by 1,266 · see citing works
mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events
Holz, M. K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2005) · Cell · doi:10.1016/j.cell.2005.10.024 · Cited by 1,262 · see citing works
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
Reitzer, L. J., Wice, B. M., & Kennell, D. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30124-2 · Cited by 1,240 · see citing works
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237 · cited 2× · see citing works
“Two key growth factor signals that regulate the mTORC1 pathway emanate from the insulin/insulin-like growth factor (IGF) 1/phosphatidyl inositol-3-OH kinase (PI(3)K) and extracellular signal regulated kinase-p90 ribosomal protein S6 kinase (ERK-RSK) pathways (Huang and Manning, 2008).”
Expression Cloning and Characterization of a Transporter for Large Neutral Amino Acids Activated by the Heavy Chain of 4F2 Antigen (CD98)
Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., & Endou, H. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.37.23629 · Cited by 1,109 · see citing works
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093 · see citing works
A nutrient sensor mechanism controls Drosophila growth
Colombani, J., Raisin, S., Pantalacci, S., Radimerski, T., Montagne, J., & Léopold, P. (2003) · Cell · doi:10.1016/s0092-8674(03)00713-x · Cited by 809 · see citing works
The RSK family of kinases: emerging roles in cellular signalling
Anjum, R., & Blenis, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2509 · Cited by 777 · see citing works
Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines
Yanagida, O., Kanai, Y., Chairoungdua, A., Kim, D. K., Segawa, H., Nii, T., Cha, S. H., Matsuo, H., Fukushima, J.-I., Fukasawa, Y., et al. (2001) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(01)00384-4 · Cited by 746 · see citing works
Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?
Fuchs, B. C., & Bode, B. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.04.005 · Cited by 717 · see citing works
Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes
Blommaart, E. F. C., Luiken, J. J. F. P., Blommaart, P. J. E., van Woerkom, G. M., & Meijer, A. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.2320 · Cited by 686 · see citing works
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake
Edinger, A. L., & Thompson, C. B. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-12-0584 · Cited by 589 · see citing works
The TOR signaling cascade regulates gene expression in response to nutrientsPreprint
Cardenas, M. E., Cutler, N. S., Lorenz, M. C., Como, C. J. D., & Heitman, J. (1999) · Genes & Development · doi:10.1101/gad.13.24.3271 · Cited by 580 · see citing works
Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family
Mastroberardino, L., Spindler, B., Pfeiffer, R., Skelly, P. J., Loffing, J., Shoemaker, C. B., & Verrey, F. (1998) · Nature · doi:10.1038/26246 · Cited by 557 · see citing works
Cloning and Functional Characterization of a System ASC-like Na+-dependent Neutral Amino Acid Transporter
Utsunomiya‐Tate, N., Endou, H., & Kanai, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14883 · Cited by 532 · see citing works
Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins
Hardwick, J. S., Kuruvilla, F. G., Tong, J. K., Shamji, A. F., & Schreiber, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14866 · Cited by 523 · see citing works
Identification and Functional Characterization of a Na+-independent Neutral Amino Acid Transporter with Broad Substrate Selectivity
Segawa, H., Fukasawa, Y., Miyamoto, K., Takeda, E., Endou, H., & Kanai, Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.28.19745 · Cited by 499 · see citing works
Selective expression of the large neutral amino acid transporter at the blood–brain barrier
Boado, R. J., Li, J. Y., Nagaya, M., Zhang, C., & Pardridge, W. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.12079 · Cited by 482 · see citing works
Atrophy of S6K1(−/−) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control
Ohanna, M., Sobering, A. K., Lapointe, T., Lorenzo, L., Praud, C., Petroulakis, E., Sonenberg, N., Kelly, P. A., Sotiropoulos, A., & Pende, M. (2005) · Nature Cell Biology · doi:10.1038/ncb1231 · Cited by 392 · see citing works
Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae
Crespo, J., & Hall, M. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.4.579-591.2002 · Cited by 389 · see citing works
The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid
Eagle, H., Oyama, V. I., Levy, M., Horton, C. L., & Fleischman, R. (1956) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65826-0 · Cited by 354 · see citing works
The Tuberous Sclerosis Protein TSC2 Is Not Required for the Regulation of the Mammalian Target of Rapamycin by Amino Acids and Certain Cellular Stresses
Smith, E. M., FINN, S. G., Tee, A. R., Browne, G. J., & Proud, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414499200 · Cited by 354 · see citing works
Amino acid availability regulates p70 S6 kinase and multiple translation factors
Wang, X., Campbell, L., Miller, C. M., & Proud, C. G. (1998) · Biochemical Journal · doi:10.1042/bj3340261 · Cited by 338 · see citing works
SKAR Links Pre-mRNA Splicing to mTOR/S6K1-Mediated Enhanced Translation Efficiency of Spliced mRNAs
Ma, X. M., Yoon, S.-O., Richardson, C. J., Jülich, K., & Blenis, J. (2008) · Cell · doi:10.1016/j.cell.2008.02.031 · Cited by 335 · see citing works
Activation of system L heterodimeric amino acid exchangers by intracellular substrates
Meier, C., Ristic, Z., Klauser, S., & Verrey, F. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.580 · Cited by 314 · see citing works
mTOR signaling to translation.
Gingras, A., Raught, B., & Sonenberg, N. (2004) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-642-18930-2_11 · Cited by 287 · see citing works
System L: heteromeric exchangers of large, neutral amino acids involved in directional transport
Verrey, F. (2003) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0973-z · Cited by 285 · see citing works
The role of glutamine in the oxidative metabolism of malignant cells.
Kovacević, Z., & Morris, H. P. (1972) · PubMed · Cited by 225 · see citing works
The amino acid sensitive TOR pathway from yeast to mammals
Dann, S. G., & Thomas, G. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.04.068 · Cited by 213 · see citing works
TOR regulation of AGC kinases in yeast and mammals
Jacinto, E., & Lorberg, A. (2008) · Biochemical Journal · doi:10.1042/bj20071518 · Cited by 201 · see citing works
Coordinate regulation of translation by the PI 3-kinase and mTOR pathways
Martin, K. A., & Blenis, J. (2002) · Advances in cancer research · doi:10.1016/s0065-230x(02)86001-8 · Cited by 199 · see citing works
Nγ-Aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site
Esslinger, C. S., Cybulski, K. A., & Rhoderick, J. F. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2004.11.028 · Cited by 151 · see citing works
Relation between glutamine, branched-chain amino acids, and protein metabolism 1 1Guest Editor: Gil Hardy, PhD
Holeček, M. (2002) · Nutrition · doi:10.1016/s0899-9007(01)00767-5 · Cited by 142 · see citing works
Absorption and metabolic effects of enterally administered glutamine in humans
Déchelotte, P., Darmaun, D., Rongier, M., et al. (1991) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1991.260.5.g677 · Cited by 137 · see citing works
The transport of glutamine into mammalian cells
John, D. M. (2006) · Frontiers in bioscience · doi:10.2741/2109 · Cited by 128 · see citing works
Thinking globally and acting locally with TOR
Arsham, A. M., & Neufeld, T. P. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.09.005 · Cited by 127 · see citing works
Stressing Out Over Survival: Glutamine as an Apoptotic Modulator
Fuchs, B. C., & Bode, B. P. (2006) · Journal of Surgical Research · doi:10.1016/j.jss.2005.07.013 · Cited by 111 · see citing works
Overexpression of glutamine synthetase in human primary liver cancer
Christa, L., Simon, M., Flinois, J.-P., Gebhardt, R., Bréchot, C., & Lasserre, C. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90024-8 · Cited by 102 · see citing works
Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products.
Wolf, D. A., Wang, S., Panzica, M. A., et al. (1996) · PubMed · Cited by 82 · see citing works
minidiscs encodes a putative amino acid transporter subunit required non-autonomously for imaginal cell proliferation
Martin, J. F., Hersperger, E., Simcox, A. A., et al. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00338-x · Cited by 78 · see citing works
Platelet‐derived growth factor stimulates LAT1 gene expression in vascular smooth muscle: Role in cell growth
Liu, X., Reyna, S. V., Ensenat, D., Peyton, K. J., Wang, H., Schafer, A. I., & Durante, W. (2004) · The FASEB Journal · doi:10.1096/fj.03-0886fje · Cited by 77 · see citing works
Self-citation
Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation
Nii, T., Segawa, H., Taketani, Y., Tani, Y., OHKIDO, M., KISHIDA, S., Ito, M., Endou, H., Kanai, Y., Takeda, E., et al. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3580693 · Cited by 74 · see citing works
A novel transiently expressed, integral membrane protein linked to cell activation. Molecular cloning via the rapid degradation signal AUUUA.
Gaugitsch, H. W., Prieschl, E. E., Kalthoff, F., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49906-7 · Cited by 57 · see citing works
Whole body and skeletal muscle glutamine metabolism in healthy subjects
Mittendorfer, B., Volpi, E., & Wolfe, R. R. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.2.e323 · Cited by 52 · see citing works
Glutamine synthetase and hepatocarcinogenesis
Rolf, G., & Williams, G. M. (1995) · Carcinogenesis · doi:10.1093/carcin/16.8.1673 · Cited by 43 · see citing works

Flagged first, then by citations

Sorted by citations

The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
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-citation
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
Self-citation
mTOR: 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
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) <sup>1</sup>
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-citation
Oxidative stress and autophagy: The clash between damage and metabolic needs
Filomeni, G., De Zio, D., & Cecconi, F. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.150 · Cited by 2,195 · see citing works
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · see citing works
“Because glutamine flux might regulate cell growth through the mTOR pathway (Nicklin et al., 2009), glutamine-dependent modulation of mTOR activation might partially account for the regulation of T cell growth by Myc.”
BackgroundInfluential
mTOR regulation of autophagy
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
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770 · 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-citation
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418 · see citing works
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
DeBerardinis, R. J., & Cheng, T. (2010) · Oncogene · doi:10.1038/onc.2009.358 · Cited by 1,365 · see citing works
Glutamine and cancer: cell biology, physiology, and clinical opportunities
Hensley, C. T., Wasti, A. T., & DeBerardinis, R. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69600 · Cited by 1,262 · see citing works
mTOR signalling and cellular metabolism are mutual determinants in cancer
Mossmann, D., Park, S., & Hall, M. N. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0074-8 · Cited by 1,088 · see citing works
Regulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035 · see citing works
Glutamine reliance in cell metabolism
Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks
Magnuson, B., Ekim, B., & Fingar, D. C. (2012) · Biochemical Journal · doi:10.1042/bj20110892 · Cited by 1,015 · see citing works
Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
Sinclair, L. V., Rolf, J., Emslie, E., Shi, Y.-B., Taylor, P. M., & Cantrell, D. A. (2013) · Nature Immunology · doi:10.1038/ni.2556 · Cited by 930 · see citing works
Glutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · 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
Glutamine Metabolism in Cancer: Understanding the Heterogeneity
Cluntun, A. A., Lukey, M. J., Cerione, R. A., & Locasale, J. W. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.01.005 · Cited by 796 · see citing works
Regulation of mTORC1 by amino acids
Bar-Peled, L., & Sabatini, D. M. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.03.003 · Cited by 773 · see citing works
Differential regulation of mTORC1 by leucine and glutamine
Jewell, J. L., Kim, Y. C., Russell, R. C., Yu, F.-X., Park, H. W., Plouffe, S. W., Tagliabracci, V. S., & Guan, K.-L. (2015) · Science · doi:10.1126/science.1259472 · Cited by 757 · see citing works
Cancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1
Rebsamen, M., Pochini, L., Stasyk, T., de Araújo, M. E. G., Galluccio, M., Kandasamy, R. K., Snijder, B., Fauster, A., Rudashevskaya, E. L., Bruckner, M., et al. (2015) · Nature · doi:10.1038/nature14107 · Cited by 673 · see citing works
The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type
Yuneva, M. O., Fan, T. W. M., Allen, T. D., Higashi, R. M., Ferraris, D. V., Tsukamoto, T., Matés, J. M., Alonso, F. J., Wang, C., Seo, Y., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2011.12.015 · Cited by 639 · see citing works
The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4
Csibi, A., Fendt, S.-M., Li, C., Poulogiannis, G., Choo, A. Y., Chapski, D. J., Jeong, S. M., Dempsey, J. M., Parkhitko, A., Morrison, T., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.023 · Cited by 586 · see citing works
Self-citation
Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target
Timmerman, L. A., Holton, T., Yuneva, M., Louie, R. J., Padró, M., Daemen, A., Hu, M., Chan, D. A., Ethier, S. P., van ‘t Veer, L. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.08.020 · Cited by 573 · see citing works
Glutathione primes t cell metabolism for inflammation
Mak, T. W., Grusdat, M., Duncan, G. S., Dostert, C., Nonnenmacher, Y., Cox, M., Binsfeld, C., Hao, Z., Brüstle, A., Itsumi, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.019 · Cited by 511 · see citing works
Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor
Krall, A. S., Xu, S., Graeber, T. G., Braas, D., & Christofk, H. R. (2016) · Nature Communications · doi:10.1038/ncomms11457 · Cited by 504 · see citing works
Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation
Klysz, D., Tai, X., Robert, P. A., Craveiro, M., Cretenet, G., Oburoglu, L., Mongellaz, C., Floess, S., Fritz, V., Matias, M. I., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aab2610 · Cited by 522 · 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
Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models
Schulte, M. L., Fu, A., Zhao, P., Li, J., Geng, L., Smith, S. T., Kondo, J., Coffey, R. J., Johnson, M. O., Rathmell, J. C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4464 · Cited by 494 · see citing works
Glutaminolysis as a target for cancer therapy
Jin, L., Alesi, G. N., & Kang, S. (2016) · Oncogene · doi:10.1038/onc.2015.447 · Cited by 459 · see citing works
Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis
Green, C. R., Wallace, M., Divakaruni, A. S., Phillips, S. A., Murphy, A. N., Ciaraldi, T. P., & Metallo, C. M. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.1961 · Cited by 471 · see citing works
Asparagine Plays a Critical Role in Regulating Cellular Adaptation to Glutamine Depletion
Zhang, J., Fan, J., Venneti, S., Cross, J. R., Takagi, T., Bhinder, B., Djaballah, H., Kanai, M., Cheng, E. H., Judkins, A. R., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.018 · Cited by 439 · see citing works
The utilization of extracellular proteins as nutrients is suppressed by mTORC1
Palm, W., Park, Y., Wright, K., Pavlova, N. N., Tuveson, D. A., & Thompson, C. B. (2015) · Cell · doi:10.1016/j.cell.2015.06.017 · Cited by 457 · see citing works
A Variant of SLC1A5 Is a Mitochondrial Glutamine Transporter for Metabolic Reprogramming in Cancer Cells
Yoo, H. C., Park, S. J., Nam, M., Kang, J., Kim, K., Yeo, J. H., Kim, J.-K., Heo, Y., Lee, H. S., Lee, M. Y., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.020 · Cited by 449 · 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
Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition
Jacque, N., Ronchetti, A. M., Larrue, C., Meunier, G., Birsen, R., Willems, L., Saland, E., Decroocq, J., Maciel, T. T., Lambert, M., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621870 · Cited by 387 · see citing works
ATF4 Regulates MYC-Mediated Neuroblastoma Cell Death upon Glutamine Deprivation
Qing, G., Li, B., Vu, A., Skuli, N., Walton, Z. E., Liu, X., Mayes, P. A., Wise, D. R., Thompson, C. B., Maris, J. M., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.09.021 · Cited by 375 · see citing works
Cancer metabolism: current perspectives and future directions
Muñoz-Pinedo, C., El Mjiyad, N., & Ricci, J.-E. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.123 · Cited by 385 · see citing works
The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism
Wellen, K. E., Lu, C., Mancuso, A., Lemons, J. M. S., Ryczko, M., Dennis, J. W., Rabinowitz, J. D., Coller, H. A., & Thompson, C. B. (2010) · Genes & Development · doi:10.1101/gad.1985910 · Cited by 377 · see citing works
Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise
Wackerhage, H., Schoenfeld, B. J., Hamilton, D. L., Lehti, M., & Hulmi, J. J. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00685.2018 · Cited by 357 · see citing works
Targeting autophagy in obesity: from pathophysiology to management
Zhang, Y., Sowers, J. R., & Ren, J. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0009-1 · Cited by 338 · see citing works
Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer
Yang, L., Moss, T., Mangala, L. S., Marini, J., Zhao, H., Wahlig, S., Armaiz‐Pena, G., Jiang, D., Achreja, A., Win, J., et al. (2014) · Molecular Systems Biology · doi:10.1002/msb.20134892 · Cited by 326 · see citing works
As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino Acid
Pavlova, N. N., Hui, S., Ghergurovich, J. M., Fan, J., Intlekofer, A. M., White, R. M., Rabinowitz, J. D., Thompson, C. B., & Zhang, J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.006 · Cited by 341 · see citing works
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes
Takahara, T., Amemiya, Y., Sugiyama, R., Maki, M., & Shibata, H. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00679-2 · Cited by 300 · see citing works
Wnt signaling and cellular metabolism in osteoblasts
Karner, C. M., & Long, F. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2425-5 · Cited by 295 · see citing works
Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9
Jung, J., Genau, H. M., & Behrends, C. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00125-15 · Cited by 266 · see citing works
Linking diet to acne metabolomics, inflammation, and comedogenesis: an update
Melnik, B. (2015) · Clinical, Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s69135 · Cited by 259 · see citing works
Glutaminolysis: Supplying carbon or nitrogen or both for cancer cells?
Dang, C. V. (2010) · Cell Cycle · doi:10.4161/cc.9.19.13302 · Cited by 245 · see citing works
MYC and tumor metabolism: chicken and egg
Dejure, F. R., & Eilers, M. (2017) · The EMBO Journal · doi:10.15252/embj.201796438 · Cited by 240 · see citing works
Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer
Sayin, V. I., LeBoeuf, S. E., Singh, S. X., Davidson, S. M., Biancur, D., Guzelhan, B. S., Alvarez, S. W., Wu, W. L., Karakousi, T. R., Zavitsanou, A. M., et al. (2017) · eLife · doi:10.7554/elife.28083 · Cited by 231 · see citing works
The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1
Hansen, C. G., Ng, Y. L. D., Lam, W.-L. M., Plouffe, S. W., & Guan, K.-L. (2015) · Cell Research · doi:10.1038/cr.2015.140 · Cited by 212 · see citing works
The L-cell in nutritional sensing and the regulation of appetite
Spreckley, E. (2015) · Frontiers in Nutrition · doi:10.3389/fnut.2015.00023 · Cited by 198 · see citing works
Uses and abuses of macropinocytosis
Bloomfield, G., & Kay, R. R. (2016) · Journal of Cell Science · doi:10.1242/jcs.176149 · Cited by 193 · see citing works
Glutamine Transport and Mitochondrial Metabolism in Cancer Cell Growth
Scalise, M., Pochini, L., Galluccio, M., Console, L., & Indiveri, C. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00306 · Cited by 183 · see citing works
Selective alanine transporter utilization creates a targetable metabolic niche in pancreatic cancer
Parker, S. J., Amendola, C. R., Hollinshead, K. E. R., Yu, Q., Yamamoto, K., Encarnación-Rosado, J., Rose, R. E., LaRue, M. M., Sohn, A. S. W., Biancur, D. E., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0959 · Cited by 175 · see citing works
Self-citation
Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon
Van Nguyen, T., Lee, J. E., Sweredoski, M. J., Yang, S.-J., Jeon, S.-J., Harrison, J. S., Yim, J.-H., Lee, S. G., Handa, H., Kuhlman, B., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.02.032 · Cited by 177 · see citing works
“Moreover, glutamine has a critical role in regulating mTOR signaling, translation, and autophagy to coordinate cell growth and proliferation (Nicklin et al., 2009).”
Influential
Glutamine: pleiotropic roles in tumor growth and stress resistance
Shanware, N. P., Mullen, A. R., DeBerardinis, R. J., & Abraham, R. T. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0731-9 · Cited by 176 · see citing works
EGFR-Pak signaling selectively regulates glutamine deprivation-induced macropinocytosis
Lee, S.-W., Zhang, Y., Jung, M., Cruz, N., Alas, B., & Commisso, C. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.05.043 · Cited by 172 · see citing works
The SIRT1/HIF2α Axis Drives Reductive Glutamine Metabolism under Chronic Acidosis and Alters Tumor Response to Therapy
Corbet, C., Draoui, N., Polet, F., Pinto, A., Drozak, X., Riant, O., & Feron, O. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0705 · Cited by 169 · see citing works
Activation of Oxidative Stress Response in Cancer Generates a Druggable Dependency on Exogenous Non-essential Amino Acids
LeBoeuf, S. E., Wu, W. L., Karakousi, T. R., Karadal, B., Jackson, S. R., Davidson, S. M., Wong, K.-K., Koralov, S. B., Sayin, V. I., & Papagiannakopoulos, T. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.012 · Cited by 150 · see citing works
Amino Acids Stimulate TORC1 through Lst4-Lst7, a GTPase-Activating Protein Complex for the Rag Family GTPase Gtr2
Péli-Gulli, M.-P., Sardu, A., Panchaud, N., Raucci, S., & De Virgilio, C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.059 · Cited by 157 · see citing works
Glutaminolysis and autophagy in cancer
Villar, V. H., Merhi, F., Djavaheri-Mergny, M., & Durán, R. V. (2015) · Autophagy · doi:10.1080/15548627.2015.1053680 · Cited by 143 · see citing works
Acetylation promotes BCAT2 degradation to suppress BCAA catabolism and pancreatic cancer growth
Lei, M.-Z., Li, X.-X., Zhang, Y., Li, J.-T., Zhang, F., Wang, Y.-P., Yin, M., Qu, J., & Lei, Q.-Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0168-0 · Cited by 129 · see citing works
Self-citation
HIF-independent role of prolyl hydroxylases in the cellular response to amino acids
Durán, R. V., MacKenzie, E. D., Boulahbel, H., Frezza, C., Heiserich, L., Tardito, S., Bussolati, O., Rocha, S., Hall, M. N., & Gottlieb, E. (2013) · Oncogene · doi:10.1038/onc.2012.465 · Cited by 139 · see citing works
Altered energy metabolism in cancer: A unique opportunity for therapeutic intervention
Zhang, Y., & Yang, J.-M. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.22958 · Cited by 132 · see citing works
<scp>TOR</scp>‐mediated regulation of metabolism in aging
Antikainen, H., Driscoll, M., Haspel, G., & Dobrowolski, R. (2017) · Aging Cell · doi:10.1111/acel.12689 · Cited by 122 · see citing works
“Several SLC proteins belonging to families capable of transporting amino acids at the plasma membrane have been shown to regulate mTORC1 activity (Nicklin et al., 2009).”
Background
Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets
Bröer, A., Fairweather, S., & Bröer, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00785 · Cited by 124 · see citing works
Macropinocytosis, mTORC1 and cellular growth control
Yoshida, S., Pacitto, R., Inoki, K., & Swanson, J. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2710-y · Cited by 114 · see citing works
Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation
Kimball, S. R., Gordon, B. S., Moyer, J. E., Dennis, M. D., & Jefferson, L. S. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.03.008 · Cited by 97 · see citing works
Regulation of muscle protein synthesis in humans
Phillips, B. E., Hill, D. S., & Atherton, P. J. (2012) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e32834d19bc · Cited by 91 · see citing works
p97/VCP promotes degradation of CRBN substrate glutamine synthetase and neosubstrates
Nguyen, T. V., Li, J., Lu, C.-C. (., Mamrosh, J. L., Lu, G., Cathers, B. E., & Deshaies, R. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700949114 · Cited by 85 · see citing works
Glutamine as an Essential Amino Acid for KRas-Driven Cancer Cells
Bernfeld, E., & Foster, D. A. (2019) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2019.03.003 · Cited by 85 · see citing works
Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in <i>Xenopus</i> oocytes
Baird, F. E., Bett, K. J., MacLean, C., Tee, A. R., Hundal, H. S., & Taylor, P. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00330.2009 · Cited by 83 · see citing works
Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism
Cacace, A., Sboarina, M., Vazeille, T., & Sonveaux, P. (2017) · Oncogene · doi:10.1038/onc.2016.364 · Cited by 76 · see citing works
GPNA inhibits the sodium-independent transport system l for neutral amino acids
Chiu, M., Sabino, C., Taurino, G., Bianchi, M. G., Andreoli, R., Giuliani, N., & Bussolati, O. (2017) · Amino Acids · doi:10.1007/s00726-017-2436-z · Cited by 77 · see citing works
Glutamine Supplementation Stimulates Protein-Synthetic and Inhibits Protein-Degradative Signaling Pathways in Skeletal Muscle of Diabetic Rats
Lambertucci, A. C., Lambertucci, R. H., Hirabara, S. M., Curi, R., Moriscot, A. S., Alba-Loureiro, T. C., Guimarães-Ferreira, L., Levada-Pires, A. C., Vasconcelos, D. A. A., Sellitti, D. F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050390 · Cited by 67 · see citing works
Proteinuria causes dysfunctional autophagy in the proximal tubule
Nolin, A. C., Mulhern, R. M., Panchenko, M. V., Pisarek-Horowitz, A., Wang, Z., Shirihai, O., Borkan, S. C., & Havasi, A. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00125.2016 · Cited by 58 · see citing works
Inhibition of <scp>SLC1A</scp>5 sensitizes colorectal cancer to cetuximab
Ma, H., Wu, Z., Peng, J., Li, Y., Huang, H., Liao, Y., Zhou, M., Sun, L., Huang, N., Shi, M., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31274 · Cited by 52 · see citing works
Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement
Barazzoni, R., Short, K. R., Asmann, Y., Coenen-Schimke, J. M., Robinson, M. M., & Sreekumaran Nair, K. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00067.2012 · Cited by 48 · see citing works
The role of glutamine in neurogenesis promoted by the green tea amino acid theanine in neural progenitor cells for brain health
Yoneda, Y., Kuramoto, N., & Kawada, K. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104505 · Cited by 39 · see citing works
The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death
Velentzas, P. D., Zhang, L., Das, G., Chang, T.-K., Nelson, C., Kobertz, W. R., & Baehrecke, E. H. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.09.015 · Cited by 31 · see citing works
Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity
van Niekerk, G., du Toit, A., Loos, B., & Engelbrecht, A.-M. (2018) · Metabolism · doi:10.1016/j.metabol.2017.12.007 · Cited by 34 · see citing works
Oral L-Glutamine Pretreatment Attenuates Skeletal Muscle Atrophy Induced by 24-h Fasting in Mice
de Vasconcelos, D. A. A., Giesbertz, P., de Souza, D. R., Vitzel, K. F., Abreu, P., Marzuca-Nassr, G. N., Fortes, M. A. S., Murata, G. M., Hirabara, S. M., Curi, R., et al. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.05.010 · Cited by 33 · see citing works
ATG12 deficiency results in intracellular glutamine depletion, abrogation of tumor hypoxia and a favorable prognosis in cancer
Keulers, T. G., Koch, A., van Gisbergen, M. W., Barbeau, L. M. O., Zonneveld, M. I., de Jong, M. C., Savelkouls, K. G. M., Wanders, R. G., Bussink, J., Melotte, V., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.2008690 · Cited by 30 · see citing works
Promotion of Both Proliferation and Neuronal Differentiation in Pluripotent P19 Cells with Stable Overexpression of the Glutamine Transporter slc38a1
Ogura, M., Kakuda, T., Takarada, T., Nakamichi, N., Fukumori, R., Kim, Y.-H., Hinoi, E., & Yoneda, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048270 · Cited by 28 · see citing works
Do Bacteria Provide an Alternative to Cancer Treatment and What Role Does Lactic Acid Bacteria Play?
Dicks, L. M. T., & Vermeulen, W. (2022) · Microorganisms · doi:10.3390/microorganisms10091733 · Cited by 25 · see citing works
An L-Glutamine transporter isoform for neurogenesis facilitated by L-Theanine
Yoneda, Y. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2317-6 · Cited by 23 · see citing works
Alterations in the gastric microbiota and metabolites in gastric cancer: An update review
Lei, C., Gong, D., Zhuang, B., & Zhang, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.960281 · Cited by 20 · see citing works
Daily oral intake of theanine prevents the decline of 5-bromo-2′-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress
Takarada, T., Nakamichi, N., Kakuda, T., Nakazato, R., Kokubo, H., Ikeno, S., Nakamura, S., Hinoi, E., & Yoneda, Y. (2015) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.12.018 · Cited by 19 · see citing works
Effect of light-load resistance exercise on postprandial amino acid transporter expression in elderly men
Agergaard, J., Bülow, J., Jensen, J. K., Reitelseder, S., Bornø, A., Drummond, M. J., Schjerling, P., & Holm, L. (2017) · Physiological Reports · doi:10.14814/phy2.13444 · Cited by 17 · see citing works
NRF3 activates mTORC1 arginine-dependently for cancer cell viability
Hirose, S., Waku, T., Tani, M., Masuda, H., Endo, K., Ashitani, S., Aketa, I., Kitano, H., Nakada, S., Wada, A., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106045 · Cited by 15 · see citing works
mTORC2 deficiency alters the metabolic profile of conventional dendritic cells
Watson, A. R., Dai, H., Zheng, Y., Nakano, R., Giannou, A. D., Menk, A. V., Stolz, D. B., Delgoffe, G. M., & Thomson, A. W. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01451 · Cited by 15 · see citing works
Selective upregulation by theanine of Slc38a1 expression in neural stem cell for brain wellness
Yoneda, Y., Kawada, K., & Kuramoto, N. (2020) · Molecules · doi:10.3390/molecules25020347 · Cited by 13 · see citing works

A genetic platform to investigate the functions of bacterial drug efflux pumps
Teelucksingh, T., Thompson, L. K., Zhu, S., Kuehfuss, N. M., Goetz, J. A., Gilbert, S., MacNair, C. R., Geddes‐McAlister, J., Brown, E. D., & Cox, G. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01119-y · Cited by 46 · see citing works
Synthesis and evaluation of fluoroquinolone derivatives as substrate-based inhibitors of bacterial efflux pumps
German, N., Wei, P., Kaatz, G. W., & Kerns, R. J. (2008) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2008.01.042 · Cited by 68 · see citing works
Efflux Pump Inhibitors: A Novel Approach to Combat Efflux-Mediated Drug Resistance in Bacteria
Wang, Y., Venter, H., & Ma, S. (2015) · Current Drug Targets · doi:10.2174/1389450116666151001103948 · Cited by 116 · see citing works
Self-citation
Why most transporter mutations that cause antibiotic resistance are to efflux pumps rather than to import transportersPreprint
Mendes, P., Girardi, E., Superti‐Furga, G., & Kell, D. B. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.16.909507 · Cited by 8 · see citing works
Glutamine stimulates mTORC1 independent of the cell content of essential amino acids
Chiu, M., Tardito, S., Barilli, A., et al. (2012) · Amino Acids · doi:10.1007/s00726-012-1312-0 · Cited by 34 · see citing works

Authors: Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V. E., MacKeigan, J. P., Porter, J. A., Wang, Y. K., Cantley, L. C., Finan, P. M., & Murphy, L. O.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Murphy, Leon O.
ORCID: Nicklin, Paul
Zhang, Bailin
Nyfeler, Beat
Yang, Haidi
Hild, Marc
Wilson, Christopher
Myer, Vic E.
MacKeigan, Jeffrey P.
Cantley, Lewis C.
Venue: Cell
Publisher: Elsevier BV
Published: 2009-02
Volume: 136
Issue: 3
Pages: 521-534
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2008.11.044
PMC: PMC3733119
OpenAlex: W2169903226
Cited by: 1,798
References: 59
Citations by year: 2026: 89 · 2025: 106 · 2024: 89 · 2023: 92 · 2022: 129 · 2021: 141 · 2020: 130 · 2019: 116 · 2018: 109 · 2017: 107 · 2016: 118 · 2015: 127 · 2014: 120 · 2013: 95 · 2012: 90
FWCI: 40.12
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1627 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
University of Hertfordshire Research Archive (University of Hertfordshire) (acceptedVersion)
University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
Funders: National Institute of General Medical Sciences (R01GM041890)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords: mTOR activation, autophagy, amino acid transport, SLC1A5, leucine, essential amino acids, mRNA translation, cell growth, cancer cells
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Animals, Autophagy, Drosophila melanogaster, Glutamine, Humans, Leucine, Protein Kinases, Proteins, Transcription Factors, Amino Acid Transport System ASC, Cell Line, Tumor, Multiprotein Complexes, 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

Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks