ArticleCell death & disease2020
Telomeric injury by KML001 in human T cells induces mitochondrial dysfunction through the p53-PGC-1α pathway.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Leukocyte Telomere Length and Cross-Sectional and Longitudinal Variations in Gray Matter Volume and Cortical Thickness.Brain and behavior · 2026Article
- Review
- Unraveling the telomere-mitochondrial axis in colorectal cancer: Results from a prospectively followed cohort.Molecular medicine (Cambridge, Mass.) · 2026Article
- Molecular Mechanisms of Accelerated Ageing in Geriatric Depression: Interplay of Telomere Attrition, Mitochondrial Dysfunction and Cellular Senescence.International journal of molecular sciences · 2026Review
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Modulation of cellular senescence in psoriatic arthritis: exploring the potential impact of bDMARDs on telomere length, mtDNA copy number, and oxidative damage.Clinical and experimental medicine · 2025Article
- p38 mitogen-activated protein kinase drives senescence in CD4Immunity & ageing : I & A · 2025Article
- miR-23a-mediated TRF2 repression in CD4 T cells from PLWH.Molecular immunology · 2025Article
- Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP/PS1 mousmodel of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types.International journal of molecular sciences · 2025Review
- Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging.Frontiers in immunology · 2025Review
- Article
- Article
- Review
- Telomere Length, Mitochondrial DNA, and Micronucleus Yield in Response to Oxidative Stress in Peripheral Blood Mononuclear Cells.International journal of molecular sciences · 2024Article
- Genomic Instability and Epigenetic Changes during Aging.International journal of molecular sciences · 2023Review
- ROS-Induced Mitochondrial Dysfunction in CD4 T Cells from ART-Controlled People Living with HIV.Viruses · 2023Article
- Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases.Stem cell reviews and reports · 2022Review
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
Telomere erosion and mitochondrial dysfunction are prominent features of aging cells with progressive declines of cellular functions. Whether telomere injury induces mitochondrial dysfunction in human T lymphocytes, the major component of adaptive host immunity against infection and malignancy, remains unclear. We have recently shown that disruption of telomere integrity by KML001, a telomere-targeting drug, induces T cell senescence and apoptosis via the telomeric DNA damage response (DDR). In this study, we used KML001 to further investigate the role and mechanism of telomere injury in mitochondrial dysregulation in aging T cells. We demonstrate that targeting telomeres by KML001 induces mitochondrial dysfunction, as evidenced by increased mitochondrial swelling and decreased mitochondrial membrane potential, oxidative phosphorylation, mitochondrial DNA content, mitochondrial respiration, oxygen consumption, glycolysis, and ATP energy production. Mechanistically, we found that the KML001-induced telomeric DDR activated p53 signaling, which in turn repressed the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor 1 (NRF-1), leading to T cell mitochondrial dysfunction. These results, forging a direct link between telomeric and mitochondrial biology, shed new light on the human T cell aging network, and demonstrate that the p53-PGC-1α-NRF-1 axis contributes to mitochondrial dysfunction in the setting of telomeric DDR. This study suggests that targeting this axis may offer an alternative, novel approach to prevent telomere damage-mediated mitochondrial and T cell dysfunctions to combat a wide range of immune aging-associated human diseases.
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