Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation
Open accessAbstract
Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival.
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?
Mitochondrial biogenesis and SHMT2/MTHFD2 expression are promoted during T-cell activation to support proliferation.
“mitochondrial biogenesis and SHMT2/MTHFD2 expression are promoted during T-cell activation to support proliferation.72”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [72]
Serine biosynthesis is necessary for T cell expansion in acquired immune responses.
“Noga et al. reported that serine biosynthesis is necessary for T cell expansion in acquired immune responses [32].”
From Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells (2022) · cites this paper as [32]
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
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088 · 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 · cited 1× · see citing works
“(F) A list of the proteins in cluster 1, representing the proteins with the greatest induction at 4 hr. Sekiya et al., 2013; Wang et al., 2011).”
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
Metallo, C. M., Gameiro, P. A., Bell, E. L., Mattaini, K. R., Yang, J., Hiller, K., Jewell, C. M., Johnson, Z. R., Irvine, D. J., Guarente, L., et al. (2012) · Nature · doi:10.1038/nature10602 · Cited by 1,791 · see citing works
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540 · see citing works
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · see citing works
Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation
Jain, M., Nilsson, R., Sharma, S., Madhusudhan, N., Kitami, T., Souza, A. L., Kafri, R., Kirschner, M. W., Clish, C. B., & Mootha, V. K. (2012) · Science · doi:10.1126/science.1218595 · Cited by 1,403 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Sena, L. A., Li, S., Jairaman, A., Prakriya, M., Ezponda, T., Hildeman, D. A., Wang, C.-R., Schumacker, P. T., Licht, J. D., Perlman, H., et al. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.020 · Cited by 1,338 · see citing works
Oxidative stress inhibits distant metastasis by human melanoma cells
Piskounova, E., Agathocleous, M., Murphy, M. M., Hu, Z., Huddlestun, S. E., Zhao, Z., Leitch, A. M., Johnson, T. M., DeBerardinis, R. J., & Morrison, S. J. (2015) · Nature · doi:10.1038/nature15726 · Cited by 1,269 · see citing works
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244 · see citing works
Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells
Sullivan, L. B., Gui, D. Y., Hosios, A. M., Bush, L. N., Freinkman, E., & Vander Heiden, M. G. (2015) · Cell · doi:10.1016/j.cell.2015.07.017 · Cited by 1,173 · see citing works
Quantitative flux analysis reveals folate-dependent NADPH production
Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014) · Nature · doi:10.1038/nature13236 · Cited by 1,114 · see citing works
Self-citationCalorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells
Berod, L., Friedrich, C., Nandan, A., Freitag, J., Hagemann, S., Harmrolfs, K., Sandouk, A., Hesse, C., Castro, C. N., Bähre, H., et al. (2014) · Nature Medicine · doi:10.1038/nm.3704 · Cited by 927 · see citing works
Carr, E. L., Kelman, A., Wu, G. S., Gopaul, R., Senkevitch, E., Aghvanyan, A., Turay, A. M., & Frauwirth, K. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903586 · Cited by 830 · see citing works
Wieman, H. L., Wofford, J. A., & Rathmell, J. C. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-07-0593 · Cited by 593 · see citing works
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Ye, J., Fan, J., Venneti, S., Wan, Y.-W., Pawel, B. R., Zhang, J., Finley, L. W. S., Lu, C., Lindsten, T., Cross, J. R., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0250 · Cited by 452 · see citing works
Self-citationDeprez, J., Vertommen, D., Alessi, D. R., Hue, L., & Rider, M. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.28.17269 · Cited by 447 · see citing works
Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.016 · Cited by 419 · see citing works
Self-citationChapter 1 Folate‐Mediated One‐Carbon Metabolism
Fox, J. T., & Stover, P. J. (2008) · Vitamins & Hormones · doi:10.1016/s0083-6729(08)00401-9 · Cited by 402 · see citing works
Kurachi, M., Barnitz, R. A., Yosef, N., Odorizzi, P. M., DiIorio, M. A., Lemieux, M. E., Yates, K. B., Godec, J., Klatt, M. G., Regev, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2834 · Cited by 384 · see citing works
Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis
Sekiya, T., Kashiwagi, I., Yoshida, R., Fukaya, T., Morita, R., Kimura, A., Ichinose, H., METZGER, D., Chambon, P., & Yoshimura, A. (2013) · Nature Immunology · doi:10.1038/ni.2520 · Cited by 314 · see citing works
Dysregulated metabolism contributes to oncogenesis
Hirschey, M. D., DeBerardinis, R. J., Diehl, A. M., Drew, J. E., Frezza, C., Green, M. F., Jones, L. W., Ko, Y. H., Le, A., Lea, M. A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.10.002 · Cited by 306 · see citing works
Herbig, K., Chiang, E. I., Lee, L.-R., Hills, J., Shane, B., & Stover, P. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205000200 · Cited by 264 · see citing works
Tedeschi, P. M., Markert, E. K., Gounder, M. K., Lin, H., Dvorzhinski, D., Dolfi, S. C., Chan, L. L.-Y., Qiu, J., DiPaola, R. S., Hirshfield, K. M., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.393 · Cited by 261 · see citing works
Mitochondrial Biogenesis through Activation of Nuclear Signaling ProteinsPreprint
Dominy, J. E., & Puigserver, P. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a015008 · Cited by 255 · see citing works
Mouse lines with photo‐activatable mitochondria to study mitochondrial dynamics
Pham, A. H., McCaffery, J. M., & Chan, D. C. (2012) · genesis · doi:10.1002/dvg.22050 · Cited by 229 · see citing works
Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria
Anderson, D. D., Quintero, C. M., & Stover, P. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103623108 · Cited by 186 · see citing works
Characterization of the Usage of the Serine Metabolic Network in Human Cancer
Mehrmohamadi, M., Liu, X., Shestov, A. A., & Locasale, J. W. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.026 · Cited by 157 · see citing works
Tsafrir, D., Tsafrir, I., Ein-Dor, L., Zuk, O., Notterman, D. A., & Domany, E. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti329 · Cited by 146 · see citing works
Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction
Martín‐Montalvo, A., & de Cabo, R. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4866 · Cited by 109 · see citing works
Finley, L. W. S., Lee, J., Souza, A., Desquiret-Dumas, V., Bullock, K., Rowe, G. C., Procaccio, V., Clish, C. B., Arany, Z., & Haigis, M. C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115813109 · Cited by 102 · see citing works
Self-citationD’Souza, A. D., Parikh, N. S., Kaech, S. M., & Shadel, G. S. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.08.001 · Cited by 99 · see citing works
A forward genetic screen reveals roles for Nfkbid , Zeb1 , and Ruvbl2 in humoral immunity
Arnold, C. N., PIRIE, E. C., Dosenovic, P., McInerney, G. M., Xia, Y., Wang, N. S., Li, X., Siggs, O. M., Hedestam, G. B. K., & Beutler, B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209134109 · Cited by 98 · see citing works
Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway
Ducker, G. S., Chen, L., Morscher, R. J., Ghergurovich, J. M., Esposito, M., Teng, X., Kang, Y., & Rabinowitz, J. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.011 · Cited by 91 · see citing works
Self-citationSirtuins and the Metabolic Hurdles in Cancer
German, N. J., & Haigis, M. C. (2015) · Current Biology · doi:10.1016/j.cub.2015.05.012 · Cited by 84 · see citing works
Self-citationMitochondrial Biogenesis in Skeletal Muscle in Response to Endurance Exercises
Freyssenet, D. G., Berthon, P. M., & Denis, C. (1996) · Archives of Physiology and Biochemistry · doi:10.1076/apab.104.2.129.12878 · Cited by 72 · see citing works
Kruschwitz, H., McDonald, D., Cossins, E. A., & Schirch, V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61970-8 · Cited by 62 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239 · see citing works
Self-citationThe multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935 · see citing works
Self-citationMetabolic Instruction of Immunity
Buck, M. D., Sowell, R., Kaech, S. M., & Pearce, E. L. (2017) · Cell · doi:10.1016/j.cell.2017.04.004 · Cited by 1,232 · see citing works
Mitochondria are the powerhouses of immunity
Mills, E. L., Kelly, B., & O'Neill, L. A. J. (2017) · Nature Immunology · doi:10.1038/ni.3704 · Cited by 1,161 · see citing works
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,023 · see citing works
Unraveling the Complex Interplay Between T Cell Metabolism and Function
Geltink, R. I. K., Kyle, R. L., & Pearce, E. L. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053019 · Cited by 821 · see citing works
Metabolic coordination of T cell quiescence and activation
Chapman, N. M., Boothby, M. R., & Chi, H. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0203-y · Cited by 749 · see citing works
The pentose phosphate pathway in health and disease
TeSlaa, T. A., Ralser, M., Fan, J., & Rabinowitz, J. D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00863-2 · Cited by 690 · see citing works
Self-citationSerine is an essential metabolite for effector T cell expansion
Ma, E. H., Bantug, G., Griss, T., Condotta, S., Johnson, R. M., Samborska, B., Mainolfi, N., Suri, V., Guak, H., Balmer, M. L., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.011 · Cited by 657 · see citing works
Metabolites and the Tumour Microenvironment: From Cellular Mechanisms to Systemic Metabolism
Elia, I., & Haigis, M. C. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00317-z · Cited by 651 · see citing works
Self-citationMitochondrial fusion, fission, and mitochondrial toxicity
Meyer, J. N., Leuthner, T. C., & Luz, A. L. (2017) · Toxicology · doi:10.1016/j.tox.2017.07.019 · Cited by 521 · see citing works
The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500 · see citing works
Self-citationMetabolic pathways in T cell activation and lineage differentiation
Almeida, L., Lochner, M., Berod, L., & Sparwasser, T. D. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.10.009 · Cited by 475 · see citing works
Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism
Angajala, A., Lim, S., Phillips, J. B., Kim, J. H., Yates, C. C., You, Z., & Tan, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01605 · Cited by 454 · see citing works
The spectrum of T cell metabolism in health and disease
Bantug, G. R., Galluzzi, L., Kroemer, G., & Hess, C. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.99 · Cited by 421 · see citing works
Mitochondrial control of immunity: beyond ATP
Mehta, M., Weinberg, S. E., & Chandel, N. S. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.66 · Cited by 398 · see citing works
An evolutionary perspective on immunometabolism
Wang, A., Luan, H. H., & Medzhitov, R. M. (2019) · Science · doi:10.1126/science.aar3932 · Cited by 387 · see citing works
Four Key Steps Control Glycolytic Flux in Mammalian Cells
Tanner, L. B., Goglia, A. G., Wei, M. H., Sehgal, T., Parsons, L. R., Park, J. O., White, E., Toettcher, J. E., & Rabinowitz, J. D. (2018) · Cell Systems · doi:10.1016/j.cels.2018.06.003 · Cited by 368 · see citing works
Self-citationMa, E. H., Verway, M. J., Johnson, R. M., Roy, D. G., Steadman, M., Hayes, S., Williams, K. S., Sheldon, R. D., Samborska, B., Kosinski, P. A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.003 · Cited by 364 · see citing works
Tan, H., Yang, K., Li, Y., Shaw, T. I., Wang, Y., Blanco, D. B., Wang, X., Cho, J.-H., Wang, H., Rankin, S., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.02.010 · Cited by 372 · see citing works
Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect
Sun, L., Suo, C., Li, S., Zhang, H., & Gao, P. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.005 · Cited by 366 · see citing works
Elia, I., Rowe, J. H., Johnson, S. E., Joshi, S., Notarangelo, G., Kurmi, K., Weiss, S. A., Freeman, G. J., Sharpe, A. H., & Haigis, M. C. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.06.008 · Cited by 362 · see citing works
Self-citationYang, L., Chu, Z., Liu, M., Zou, Q., Li, J., Liu, Q., Wang, Y., Wang, T., Xiang, J., & Wang, B. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01453-1 · Cited by 362 · see citing works
Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming
Roy, D. G., Chen, J., Mamane, V. H., Ma, E. H., Muhire, B. M., Sheldon, R. D., Shorstova, T., Koning, R., Johnson, R. M., Esaulova, E., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.01.006 · Cited by 347 · see citing works
Metabolism as a guiding force for immunity
Jung, J., Zeng, H., & Horng, T. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0217-x · Cited by 345 · see citing works
Serine Metabolism Supports Macrophage IL-1β Production
Rodriguez, A. E., Ducker, G. S., Billingham, L. K., Martinez, C. A., Mainolfi, N., Suri, V., Friedman, A. A., Manfredi, M. G., Weinberg, S. E., Rabinowitz, J. D., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.014 · Cited by 346 · see citing works
Self-citationThe tumor microenvironment as a metabolic barrier to effector T cells and immunotherapy
Lim, A. R., Rathmell, W. K., & Rathmell, J. C. (2020) · eLife · doi:10.7554/elife.55185 · Cited by 330 · see citing works
Immunometabolic Interplay in the Tumor Microenvironment
Kaymak, I., Williams, K. S., Cantor, J. R., & Jones, R. G. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.09.004 · Cited by 330 · see citing works
Metabolic interventions in the immune response to cancer
O’Sullivan, D., Sanin, D. E., Pearce, E. J., & Pearce, E. L. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0140-9 · Cited by 314 · see citing works
Mechanisms of mitochondrial respiratory adaptation
Bennett, C. F., Latorre‐Muro, P., & Puigserver, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00506-6 · Cited by 313 · see citing works
Metabolic adaptation of lymphocytes in immunity and disease
Chapman, N. M., & Chi, H.-B. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.012 · Cited by 263 · see citing works
Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling
Waters, L. R., Ahsan, F. M., Wolf, D. M., Shirihai, O. S., & Teitell, M. A. (2018) · iScience · doi:10.1016/j.isci.2018.07.005 · Cited by 298 · see citing works
Geltink, R. I. K., O’Sullivan, D., Corrado, M., Bremser, A., Buck, M. D., Buescher, J. M., Firat, E., Zhu, X., Niedermann, G., Caputa, G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.08.018 · Cited by 294 · see citing works
Mitochondrial translation requires folate-dependent tRNA methylation
Morscher, R. J., Ducker, G. S., Li, H., Mayer, J., Gitai, Z., Sperl, W., & Rabinowitz, J. D. (2018) · Nature · doi:10.1038/nature25460 · Cited by 278 · see citing works
Self-citationSignaling networks in immunometabolism
Saravia, J., Raynor, J. L., Chapman, N. M., Lim, S. A., & Chi, H. (2020) · Cell Research · doi:10.1038/s41422-020-0301-1 · Cited by 252 · see citing works
The ins and outs of serine and glycine metabolism in cancer
Geeraerts, S. L., Heylen, E., Keersmaecker, K. D., & Kampen, K. R. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00329-9 · Cited by 250 · see citing works
Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function
Kurniawan, H., Franchina, D. G., Guerra, L., Bonetti, L., Soriano‐Baguet, L., Grusdat, M., Schlicker, L., Hunewald, O. E., Dostert, C., Merz, M. P., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.03.004 · Cited by 245 · see citing works
Cellular metabolism regulates the differentiation and function of T-cell subsets
Ma, S., Ming, Y., Wu, J., & Cui, G. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01148-8 · Cited by 258 · see citing works
Targeting memory T cell metabolism to improve immunity
Corrado, M., & Pearce, E. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148546 · Cited by 234 · see citing works
Suppression by TFR cells leads to durable and selective inhibition of B cell effector function
Sage, P. T., Ron‐Harel, N., Juneja, V. R., Sen, D. R., Maleri, S., Sungnak, W., Kuchroo, V. K., Haining, W. N., Chevrier, N., Haigis, M. C., et al. (2016) · Nature Immunology · doi:10.1038/ni.3578 · Cited by 236 · see citing works
Self-citationSHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation
Yang, X. P., Wang, Z., Li, X., Liu, B., Liu, M., Liu, L., Chen, S., Ren, M., Wang, Y., Yu, M., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1912 · Cited by 231 · see citing works
Metabolic Control of CD8+ T Cell Fate Decisions and Antitumor Immunity
Zhang, L., & Romero, P. J. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.11.005 · Cited by 233 · see citing works
Formate metabolism in health and disease
Pietzke, M., Meiser, J., & Vazquez, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2019.05.012 · Cited by 218 · see citing works
Dynamics in protein translation sustaining T cell preparedness
Wolf, T., Jin, W., Zoppi, G., Vogel, I. A., Akhmedov, M., Bleck, C. K. E., Beltraminelli, T., Rieckmann, J. C., Ramirez, N. J., Benevento, M., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0714-5 · Cited by 220 · see citing works
MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function
Sugiura, A., Andrejeva, G., Voss, K., Heintzman, D. R., Xu, X., Madden, M. Z., Ye, X., Beier, K. L., Chowdhury, N. U., Wolf, M. M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.10.011 · Cited by 219 · see citing works
Self-citationA small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway
Ghergurovich, J. M., García‐Cañaveras, J. C., Wang, J. Z., Schmidt, E. N., Zhang, Z., TeSlaa, T. A., Patel, H., Chen, L., Britt, E. C., Piqueras-Nebot, M., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0533-x · Cited by 211 · see citing works
Self-citationEpstein–Barr virus reprograms human B lymphocytes immediately in the prelatent phase of infection
Mrozek-Gorska, P., Buschle, A., Pich, D., Schwarzmayr, T., Fechtner, R., Scialdone, A., & Hammerschmidt, W. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901314116 · Cited by 210 · see citing works
Marchingo, J. M., Sinclair, L. V., Howden, A. J. M., & Cantrell, D. A. (2020) · eLife · doi:10.7554/elife.53725 · Cited by 202 · see citing works
T Cell Activation Depends on Extracellular Alanine
Ron‐Harel, N., Ghergurovich, J. M., Notarangelo, G., LaFleur, M. W., Tsubosaka, Y., Sharpe, A. H., Rabinowitz, J. D., & Haigis, M. C. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.034 · Cited by 199 · see citing works
Self-citationvan Bruggen, J. A. C., Martens, A. W. J., Fraietta, J. A., Hofland, T., Tonino, S. H., Eldering, E., Levin, M.-D., Siska, P. J., Endstra, S., Rathmell, J. C., et al. (2019) · Blood · doi:10.1182/blood.2018885863 · Cited by 187 · see citing works
Age-associated remodeling of T cell immunity and metabolism
Han, S., Georgiev, P., Ringel, A. E., Sharpe, A. H., & Haigis, M. C. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.005 · Cited by 193 · see citing works
Self-citationPharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells
Drijvers, J. M., Gillis, J. E., Muijlwijk, T., Nguyen, T. H., Gaudiano, E. F., Harris, I. S., LaFleur, M. W., Ringel, A. E., Yao, C.-H., Kurmi, K., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0384 · Cited by 190 · see citing works
Self-citationEpstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation
Wang, L. W., Shen, H., Nobre, L., Ersing, I., Paulo, J. A., Trudeau, S., Wang, Z., Smith, N. A., Ma, Y., Reinstadler, B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.003 · Cited by 190 · see citing works
Self-citationShin, B., Benavides, G. A., Geng, J., Koralov, S. B., Hu, H., Darley-Usmar, V. M., & Harrington, L. E. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.022 · Cited by 178 · see citing works
Huang, L.-J., Mao, X.-T., Li, Y., Liu, D.-D., Fan, K.-Q., Liu, R., Wu, T.-T., Wang, H., Zhang, Y., Yang, B., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.07.004 · Cited by 183 · see citing works
Tarasenko, T. N., Pacheco, S. E., Koenig, M. K., Gómez‐Rodríguez, J., Kapnick, S. M., Díaz, F., Zerfas, P. M., Barca, E., Sudderth, J., DeBerardinis, R. J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.007 · Cited by 177 · see citing works
Myeloid-derived itaconate suppresses cytotoxic CD8+ T cells and promotes tumour growth
Zhao, H., Teng, D., Yang, L., Xu, X., Chen, J., Jiang, T., Feng, A. Y., Zhang, Y., Frederick, D. T., Gu, L., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00676-9 · Cited by 173 · see citing works
Self-citationProtein synthesis, degradation, and energy metabolism in T cell immunity
Marchingo, J. M., & Cantrell, D. A. (2022) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00792-8 · Cited by 169 · see citing works
Serine metabolism orchestrates macrophage polarization by regulating the IGF1–p38 axis
Shan, X., Hu, P., Ni, L., Shen, L., Zhang, Y., Ji, Z., Cui, Y., Guo, M., Wang, H., Ran, L., et al. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00925-7 · Cited by 167 · see citing works
Mitochondrial activity in T cells
Desdín-Micó, G., Soto‐Heredero, G., & Mittelbrunn, M. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.10.006 · Cited by 162 · see citing works
Nitrogen Metabolism in Cancer and Immunity
Kurmi, K., & Haigis, M. C. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.02.005 · Cited by 161 · see citing works
Self-citationA guide to interrogating immunometabolism
Voss, K., Hong, H. S., Bader, J. E., Sugiura, A., Lyssiotis, C. A., & Rathmell, J. C. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00529-8 · Cited by 162 · see citing works
Asano, K., Suzuki, T., Saito, A., Wei, F., Ikeuchi, Y., Numata, T., Tanaka, R., YAMANE, Y., Yamamoto, T., Goto, T., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky068 · Cited by 159 · see citing works
Mohanty, A., Tiwari-Pandey, R., & Pandey, N. R. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00507-9 · Cited by 157 · see citing works
Mitochondrial Metabolism Regulation of T Cell–Mediated Immunity
Steinert, E. M., Vasan, K., & Chandel, N. S. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-082015 · Cited by 154 · see citing works
Ron‐Harel, N., Notarangelo, G., Ghergurovich, J. M., Paulo, J. A., Sage, P. T., Santos, D., Satterstrom, F. K., Gygi, S. P., Rabinowitz, J. D., Sharpe, A. H., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804149115 · Cited by 150 · see citing works
Self-citationSun, D.-Y., Hu, Y., Li, X., Peng, J., Dai, Z., & Wang, S. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113392 · Cited by 150 · see citing works
Ancillary Activity: Beyond Core Metabolism in Immune Cells
Puleston, D. J., Villa, M., & Pearce, E. L. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.019 · Cited by 146 · see citing works
Shen, L., Hu, P., Zhang, Y., Ji, Z., Shan, X., Ni, L., Ning, N., Wang, J., Tian, H., Shui, G., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.006 · Cited by 148 · see citing works
Fatty acid metabolism in CD 8 + T cell memory: Challenging current concepts
Raud, B., McGuire, P. J., Jones, R. G., Sparwasser, T. D., & Berod, L. (2018) · Immunological Reviews · doi:10.1111/imr.12655 · Cited by 150 · see citing works
The immunologic Warburg effect: Evidence and therapeutic opportunities in autoimmunity
Kornberg, M. (2020) · Wiley Interdisciplinary Reviews: Systems Biology and Medicine · doi:10.1002/wsbm.1486 · Cited by 118 · see citing works
Extracellular acidosis restricts one-carbon metabolism and preserves T cell stemness
Cheng, H., Qiu, Y., Xu, Y., Chen, L., Ma, K., Tao, M., Frankiw, L. S., Yin, H., Xie, E., Pan, X., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-022-00730-6 · Cited by 144 · see citing works
Targeting mitochondria in cancer: current concepts and immunotherapy approaches
Pustylnikov, S., Costabile, F., Beghi, S., & Facciabene, A. (2018) · Translational research · doi:10.1016/j.trsl.2018.07.013 · Cited by 137 · see citing works
The essential functions of mitochondrial dynamics in immune cells
Xie, J.-H., Li, Y., & Jin, J. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-0480-1 · Cited by 133 · see citing works
The complexity of the serine glycine one-carbon pathway in cancer
Reina‐Campos, M., Díaz-Meco, M. T., & Moscat, J. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201907022 · Cited by 123 · see citing works
Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome
Hoffman, J. D., Parikh, I. J., Green, S., Chlipala, G., Mohney, R., Keaton, M. A., Bauer, B., Hartz, A., & Lin, A.-L. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00298 · Cited by 120 · see citing works
Palmer, C. S., Anderson, A. J., & Stojanovski, D. (2020) · FEBS Letters · doi:10.1002/1873-3468.14022 · Cited by 120 · see citing works
Almeida, L., Dhillon-LaBrooy, A., Carriche, G. M., Berod, L., & Sparwasser, T. D. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.03.033 · Cited by 112 · see citing works
Myers, S. A., Rhoads, A., Cocco, A. R., Peckner, R., Haber, A. L., Schweitzer, L. D., Krug, K., Mani, D. R., Clauser, K. R., Rozenblatt–Rosen, O., et al. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra118.001259 · Cited by 103 · see citing works
Targeting nucleotide metabolism as the nexus of viral infections, cancer, and the immune response
Ariav, Y., Ch’ng, J., Christofk, H. R., Ron‐Harel, N., & Erez, A. (2021) · Science Advances · doi:10.1126/sciadv.abg6165 · Cited by 109 · see citing works
Self-citationGnanaprakasam, J. R., Wu, R., & Wang, R. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01075 · Cited by 105 · see citing works
Clerc, I., Moussa, D. A., Vahlas, Z., Tardito, S., Oburoglu, L., Hope, T. J., Sitbon, M., Dardalhon, V., Mongellaz, C., & Taylor, N. N. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0084-1 · Cited by 99 · see citing works
Age-related mitochondrial dysfunction as a key factor in COVID-19 disease
Fernández‐Ayala, D. J. M., Navas, P., & López‐Lluch, G. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111147 · Cited by 105 · see citing works
Regulatory mechanisms of one-carbon metabolism enzymes
Petrova, B., Maynard, A. G., Wang, P., & Kanarek, N. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105457 · Cited by 103 · see citing works
Nakajima, Y., Chamoto, K., Oura, T., & Honjo, T. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2103730118 · Cited by 100 · see citing works
Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells
Huang, Y., Si, X., Shao, M., Teng, X., Xiao, G., & Huang, H. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01255-x · Cited by 101 · see citing works
Metabolic Stress in the Immune Function of T Cells, Macrophages and Dendritic Cells
Domblides, C., Lartigue, L., & Faustin, B. (2018) · Cells · doi:10.3390/cells7070068 · Cited by 98 · see citing works
Metabolic determination of cell fate through selective inheritance of mitochondria
Döhla, J., Kuuluvainen, E., Gebert, N., Amaral, A. I., Englund, J. I., Gopalakrishnan, S., Konovalova, S. A., Nieminen, A. I., Salminen, E. S., Torregrosa‐Muñumer, R., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-021-00837-0 · Cited by 95 · see citing works
Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells
Walker, M., Lareau, C. A., Ludwig, L. S., Karaa, A., Sankaran, V. G., Regev, A., & Mootha, V. K. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001265 · Cited by 87 · see citing works
Nutrients: Signal 4 in T cell immunity
Raynor, J. L., & Chi, H. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221839 · Cited by 94 · see citing works
Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
Nam, K. N., Mounier, A., Wolfe, C. M., Fitz, N. F., Carter, A. Y., Castranio, E. L., Kamboh, H., Reeves, V. L., Wang, J., Han, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-04412-2 · Cited by 94 · see citing works
Impact of T cell characteristics on CAR-T cell therapy in hematological malignancies
Tao, Z., Chyra, Z., Kotulová, J., Celichowski, P., Mihályová, J., Charvátová, S., & Hájek, R. (2024) · Blood Cancer Journal · doi:10.1038/s41408-024-01193-6 · Cited by 96 · see citing works
Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity
Qiu, Y., Su, Y., Xie, E., Cheng, H., Du, J., Xu, Y., Pan, X., Wang, Z., Chen, D. G., Hong, Z., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.11.003 · Cited by 93 · see citing works
Hallmarks of T-cell Exit from Quiescence
Chapman, N. M., & Chi, H. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0605 · Cited by 87 · see citing works
Almeida, L., Dhillon-LaBrooy, A., Castro, C. N., Adossa, N. A., Carriche, G. M., Guderian, M., Lippens, S., Dennerlein, S., Hesse, C., Lambrecht, B. N., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.001 · Cited by 89 · see citing works
1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer
Kilgour, M. K., MacPherson, S., Zacharias, L. G., Ellis, A. E., Sheldon, R. D., Liu, E. Y., Keyes, S., Pauly, B., Carleton, G. A., Allard, B., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe1174 · Cited by 86 · see citing works
Amino acids: key sources for immunometabolites and immunotransmitters
Miyajima, M. (2020) · International Immunology · doi:10.1093/intimm/dxaa019 · Cited by 88 · see citing works
Optimization of metabolism to improve efficacy during CAR-T cell manufacturing
Zhang, M., Jin, X. K., Sun, R., Xiong, X., Wang, J., Xie, D., & Zhao, M. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03165-x · Cited by 87 · see citing works
Bioorthogonal photocatalytic proximity labeling in primary living samples
Liu, Z., Guo, F., Zhu, Y., Qin, S., Hou, Y., Guo, H., Lin, F., Chen, P. R., & Fan, X. (2024) · Nature Communications · doi:10.1038/s41467-024-46985-3 · Cited by 84 · see citing works
Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation
Jones, N., Cronin, J., Dolton, G. M., Panetti, S., Schauenburg, A. J. A., Galloway, S. A. E., Sewell, A. K., Cole, D. K., Thornton, C. A., & Francis, N. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01516 · Cited by 83 · see citing works
- Authors
- Ron-Harel, N., Santos, D., Ghergurovich, J. M., Sage, P. T., Reddy, A., Lovitch, S. B., Dephoure, N., Satterstrom, F. K., Sheffer, M., Spinelli, J. B., Gygi, S., Rabinowitz, J. D., Sharpe, A. H., & Haigis, M. C.
- Affiliations
- Harvard University (US)
- Princeton University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Haigis, Marcia C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 24
- Issue
- 1
- Pages
- 104-117
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5330619
- OpenAlex
- W2472560175
- Cited by
- 429
- References
- 41
- Citations by year
- 2026: 41 · 2025: 57 · 2024: 63 · 2023: 42 · 2022: 40 · 2021: 51 · 2020: 47 · 2019: 29 · 2018: 27 · 2017: 25 · 2016: 7
- FWCI
- 15.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (T32HG003284)
- National Institute of Allergy and Infectious Diseases (HHSN272201100018C)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103295, T32DK007260)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- mitochondrial biogenesis, one-carbon metabolism, T cell activation, CD4+ T cells, serine catabolism, SHMT2, purine biosynthesis, thymidine synthesis, T cell proliferation, T cell survival, metabolic reprogramming
- MeSH terms
- Animals, Epitopes, Organelle Biogenesis, Carbon, Cell Survival, Energy Metabolism, Lymphocyte Activation, Mice, Inbred C57BL, Mitochondria, Pyrimidines, T-Lymphocytes, CD4-Positive T-Lymphocytes, Proteome, Proteomics, Metabolic Networks and Pathways
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
