The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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.
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“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]
In the citing paper
“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]
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The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
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The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
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“(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
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Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
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Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
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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 · cited 1×
“Upon naive T cell activation, signaling pathways downstream of the T cell receptor through Erk and downstream of the CD28 costimulatory receptor through phosphatidylinositol 30-kinase (PI3K)/Akt stimulate glucose and glutamine uptake and metabolism (Carr et al., 2010; Frauwirth et al., 2002).”
BackgroundMetabolite 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
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
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Metadata
- 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
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