ArticleNature communications2023
Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 216 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
216 citing papers in PubMed, 1 synthesis or guideline pooled it, 233 citations in OpenAlex.
- Hyperbaric oxygen therapy modulates immune effector responses and reshapes peripheral immune tolerance: a narrative review.Frontiers in immunology · 2026Pooled it
- Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer.Journal of translational medicine · 2025Trial
- Article
- Chemo-metallo nanodrivers for spatiotemporally controlled in situ vaccination.Science advances · 2026Article
- Review
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Pathogenic mutations in ATAD3A cause dysregulation of RagC/D-TFEB axis and disrupt lysosomal homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Immunomodulatory Nanozymes as Programmable Redox-Immune Set-Point Regulators.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Mitochondrial metabolism and PD-1 blockade: mechanisms and therapeutic opportunities in cancer immunotherapy.Molecular biology reports · 2026Review
- Metabolic rewiring of the dendritic cell-T cell axis: tumour-derived barriers and therapeutic opportunities.Experimental & molecular medicine · 2026Review
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- The Glucose Transporter GLUT3 Controls Regulatory T Cell Function.European journal of immunology · 2026Article
- Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026Review
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Emerging Roles for Metabolism in Myocardial Inflammation During Heart Failure.Immunological reviews · 2026Review
- The impact of T cell exhaustion in hematopoietic stem cell transplantation.Stem cell research & therapy · 2026Review
- Immunometabolic Remodeling in Ischemic and Non-Ischemic Heart Failure.Journal of cardiovascular translational research · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
156 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.