Buck, M. D., O’Sullivan, D. & Pearce, E. L. T cell metabolism drives immunity. J. Exp. Med. 212, 1345–1360 (2015).
Bailis, W. et al. Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function. Nature 571, 403–407 (2019).
Xu, T. et al. Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism. Nature 548, 228–233 (2017).
Giacomello, M., Pyakurel, A., Glytsou, C. & Scorrano, L. The cell biology of mitochondrial membrane dynamics. Nat. Rev. Mol. Cell Biol. 21, 204–224 (2020).
Martinez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).
Cogliati, S. et al. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155, 160–171 (2013).
Ye, D., Guan, K. L. & Xiong, Y. Metabolism, activity, and targeting of d– and l-2-hydroxyglutarates. Trends Cancer 4, 151–165 (2018).
Chan, D. C. Mitochondrial dynamics and its involvement in disease. Annu. Rev. Pathol. 15, 235–259 (2020).
Youle, R. J. & van der Bliek, A. M. Mitochondrial fission, fusion, and stress. Science 337, 1062–1065 (2012).
Matilainen, O., Quiros, P. M. & Auwerx, J. Mitochondria and epigenetics—crosstalk in homeostasis and stress. Trends Cell Biol. 27, 453–463 (2017).
Herkenne, S. et al. Developmental and tumor angiogenesis requires the mitochondria-shaping protein Opa1. Cell Metab. 31, 987–1003.e1008 (2020).
Song, Z., Chen, H., Fiket, M., Alexander, C. & Chan, D. C. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J. Cell Biol. 178, 749–755 (2007).
Ishihara, N., Fujita, Y., Oka, T. & Mihara, K. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. EMBO J. 25, 2966–2977 (2006).
MacVicar, T. & Langer, T. OPA1 processing in cell death and disease—the long and short of it. J. Cell Sci. 129, 2297–2306 (2016).
Korn, T., Bettelli, E., Oukka, M. & Kuchroo, V. K. IL-17 and Th17 Cells. Annu. Rev. Immunol. 27, 485–517 (2009).
Wagner, A. et al. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 184, 4168–4185.e4121 (2021).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Sano, T. et al. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163, 381–393 (2015).
Hirota, K. et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat. Immunol. 12, 255–263 (2011).
Esplugues, E. et al. Control of TH17 cells occurs in the small intestine. Nature 475, 514–518 (2011).
Birsoy, K. et al. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature 508, 108–112 (2014).
Arguello, R. J. et al. SCENITH: a flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab. 32, 1063–1075.e1067 (2020).
Gaublomme, J. T. et al. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell 163, 1400–1412 (2015).
Bao, X. R. et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells. eLife 5, e10575 (2016).
Nikkanen, J. et al. Mitochondrial DNA replication defects disturb cellular dNTP pools and remodel one-carbon metabolism. Cell Metab. 23, 635–648 (2016).
Birsoy, K. et al. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 162, 540–551 (2015).
Sullivan, L. B. et al. Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 162, 552–563 (2015).
Wu, L. et al. Niche-selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy. Cell 182, 641–654.e620 (2020).
Berod, L. et al. De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat. Med. 20, 1327–1333 (2014).
Locasale, J. W. et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet. 43, 869–874 (2011).
Blagih, J., Krawczyk, C. M. & Jones, R. G. LKB1 and AMPK: central regulators of lymphocyte metabolism and function. Immunol Rev 249, 59–71 (2012).
MacIver, N. J. et al. The liver kinase B1 is a central regulator of T cell development, activation, and metabolism. J. Immunol. 187, 4187–4198 (2011).
He, N. et al. Metabolic control of regulatory T cell (Treg) survival and function by Lkb1. Proc. Natl Acad. Sci. USA 114, 12542–12547 (2017).
Yang, K. et al. Homeostatic control of metabolic and functional fitness of Treg cells by LKB1 signalling. Nature 548, 602–606 (2017).
Kottakis, F. et al. LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539, 390–395 (2016).
Shackelford, D. B. & Shaw, R. J. The LKB1–AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563–575 (2009).
Tiainen, M., Ylikorkala, A. & Makela, T. P. Growth suppression by Lkb1 is mediated by a G1 cell cycle arrest. Proc. Natl Acad. Sci. USA 96, 9248–9251 (1999).
Kullmann, L. & Krahn, M. P. Controlling the master-upstream regulation of the tumor suppressor LKB1. Oncogene 37, 3045–3057 (2018).
Fan, J. et al. Human phosphoglycerate dehydrogenase produces the oncometabolite d-2-hydroxyglutarate. ACS Chem. Biol. 10, 510–516 (2015).
Intlekofer, A. M. et al. Hypoxia induces production of l-2-hydroxyglutarate. Cell Metab. 22, 304–311 (2015).
Intlekofer, A. M. et al. l-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH. Nat. Chem. Biol. 13, 494–500 (2017).
Yang, L. et al. Serine catabolism feeds NADH when respiration is impaired. Cell Metab. 31, 809–821.e806 (2020).
Buck, M. D. et al. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell 166, 63–76 (2016).
Faubert, B. et al. Loss of the tumor suppressor LKB1 promotes metabolic reprogramming of cancer cells via HIF-1α. Proc. Natl Acad. Sci. USA 111, 2554–2559 (2014).
Johnson, M. O. et al. Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism. Cell 175, 1780–1795.e1719 (2018).
Baksh, S. C. & Finley, L. W. S. Metabolic coordination of cell fate by α-ketoglutarate-dependent dioxygenases. Trends Cell Biol. 31, 24–36 (2021).
Buck, M. D., Sowell, R. T., Kaech, S. M. & Pearce, E. L. Metabolic instruction of immunity. Cell 169, 570–586 (2017).
Reinhardt, R. L., Liang, H. E. & Locksley, R. M. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat. Immunol. 10, 385–393 (2009).
Mohrs, K., Wakil, A. E., Killeen, N., Locksley, R. M. & Mohrs, M. A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity 23, 419–429 (2005).
Wan, Y. Y. & Flavell, R. A. Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc. Natl Acad. Sci. USA 102, 5126–5131 (2005).
Sinclair, L. V., Neyens, D., Ramsay, G., Taylor, P. M. & Cantrell, D. A. Single cell analysis of kynurenine and system L amino acid transport in T cells. Nat. Commun. 9, 1981 (2018).
Ramirez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57 (2009).
Buenrostro, J. D., Wu, B., Chang, H. Y. & Greenleaf, W. J. ATAC–seq: a method for assaying chromatin accessibility genome-wide. Curr. Protoc. Mol. Biol. 109, 21.29.21–21.29.29 (2015).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
Lun, A. T. & Smyth, G. K. De novo detection of differentially bound regions for ChIP-seq data using peaks and windows: controlling error rates correctly. Nucleic Acids Res. 42, e95 (2014).
Lun, A. T. & Smyth, G. K. csaw: a Bioconductor package for differential binding analysis of ChIP-seq data using sliding windows. Nucleic Acids Res. 44, e45 (2016).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
Musa, Y. R., Boller, S., Puchalska, M., Grosschedl, R. & Mittler, G. Comprehensive proteomic investigation of Ebf1 heterozygosity in pro-B lymphocytes utlizing data independent acquisition. J. Proteome Res. 17, 76–85 (2018).
More News
Who will make AlphaFold3 open source? Scientists race to crack AI model
These crows have counting skills previously only seen in people
Seed-stashing chickadees overturn ideas about location memory