Year: 2025
Type: article
Abstract: T cell immunity deteriorates with age, accompanied by a decline in autophagy and asymmetric cell division. Here we show that autophagy regulates mitochondrial inheritance in CD8 + T cells. Using a mouse model that enables sequential tagging of mitochondria in mother and daughter cells, we demonstrate that autophagy-deficient T cells fail to clear premitotic old mitochondria and inherit them symmetrically. By contrast, autophagy-competent cells that partition mitochondria asymmetrically produce daughter cells with distinct fates: those retaining old mitochondria exhibit reduced memory potential, whereas those that have not inherited old mitochondria and exhibit higher mitochondrial turnover are long-lived and expand upon cognate-antigen challenge. Multiomics analyses suggest that early fate divergence is driven by distinct metabolic programmes, with one-carbon metabolism activated in cells retaining premitotic mitochondria. These findings advance our understanding of how T cell diversity is imprinted early during division and support the development of strategies to modulate T cell function.
Source: Nature Cell Biology
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Science Foundation, European Molecular Biology Organization, University of Dundee, Wellcome Trust, Kennedy Trust for Rheumatology Research, University of Oxford, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Helmholtz Association, Horizon 2020 Framework Programme
Awards: The contribution of degradation machineries to asymmetric cell division and T cell differentiation, Impact of autophagy on lymphocyte stemness, The role of degradation pathways on cell stemness and fate determination, Proteostasis and Autophagy in Immune Senescence, Research in particle physics and detector technology, Impact of autophagy on lymphocyte stemness, G434337789, G4717428978, The role of autophagy in quiescence of healthy hematopoietic cells., The role of autophagy in quiescence of healthy hematopoietic cells., G548224188, Strategy of piliated meningococci to cross multicellular defense barriers, Oxford - Immunology, Infection and Translational Medicine, G7723841279, G7950119664, Oxford - Immunology, Infection and Translational Medicine, G8266702520, G9000067200
OpenAlex ID: W4417492485