ArticleScience immunology2022
Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
- Macrophage trained immunity requires a mitochondrial glutamine-restriction checkpoint for antitumor protection in mice.Nature communications · 2026Article
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- CIITA/PRMT5 promote CD4BMC medicine · 2026Article
- OGDH primes macrophage for M1-like polarization and ferroptosis in sepsis associated acute lung injury.Respiratory research · 2026Article
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Spatial multiomics profiling reveals ZFP36-mediated immunometabolic reprogramming in bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Tissue Immunometabolism in Autoimmunity.European journal of immunology · 2026Review
- Succinate-mediated metabolic alterations and signaling in RA: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Microbiota-driven epigenetic programming of local immunity.Frontiers in immunology · 2026Review
- Mitochondrial complex II orchestrates divergent effects in CD4+ and CD8+ T cells.The Journal of clinical investigation · 2025Article
- Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation.Nature communications · 2025Article
- Cuproptosis Signature Would Reveal the Acute-Remitting Pattern in Patients with Neuromyelitis Optica Spectrum Disorder.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Moxibustion Alleviates Inflammation via SIRT5-mediated Post-translational Modification and Macrophage Polarization.Inflammation · 2025Article
- TCA cycle-derived oncometabolites in cancer and the immune microenvironment.Journal of biomedical science · 2025Review
- A Nanoformulation of Ubiquinol and Selenium Promotes Proliferation of Human Induced Pluripotent Stem Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin. By using complementary genetic, epigenetic, and metabolic approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic processes while controlling the ratio of succinate/α-ketoglutarate (α-KG) to modulate the activities of dioxygenases that are critical for driving T cell inflammation. In contrast to cancer cells, where succinate dehydrogenase (SDH)/complex II inactivation drives cell transformation and growth, SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, blocking carbon flux to support nucleoside biosynthesis. Replenishing the intracellular nucleoside pool partially relieved the dependence of T cells on SDH/complex II for proliferation and survival. SDH deficiency induced a proinflammatory gene signature in T cells and promoted T helper 1 and T helper 17 lineage differentiation. An increasing succinate/α-KG ratio in SDH-deficient T cells promoted inflammation by changing the pattern of the transcriptional and chromatin accessibility signatures and consequentially increasing the expression of the transcription factor, PR domain zinc finger protein 1. Collectively, our studies revealed a role of SDH/complex II in allocating carbon resources for anabolic processes and epigenetic regulation in T cell proliferation and inflammation.
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Registered trials
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