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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]
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“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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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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