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| Item Type: | Article |
|---|---|
| Title: | Autophagy-regulated mitochondrial inheritance controls early CD8(+) T cell fate commitment |
| Creators: |
Borsa, Mariana  ORCID: https://orcid.org/0000-0003-1519-2597, Lechuga-Vieco, Ana Victoria ORCID: https://orcid.org/0000-0001-5546-9752, Kayvanjoo, Amir H. ORCID: https://orcid.org/0000-0003-1315-8336, Jenkins, Edward, Yazicioglu, Yavuz, Compeer, Ewoud B. ORCID: https://orcid.org/0000-0002-3050-7633, Richter, Felix C., Rapp, Simon ORCID: https://orcid.org/0000-0002-5141-0611, Mitchell, Robert, Youdale, Tom, Bui, Hien, Kuuluvainen, Emilia, Dustin, Michael L. ORCID: https://orcid.org/0000-0003-4983-6389, Sinclair, Linda V. ORCID: https://orcid.org/0000-0003-1248-7189, Katajisto, Pekka ORCID: https://orcid.org/0000-0002-3033-4189 and Simon, Anna Katharina ORCID: https://orcid.org/0000-0002-4077-7995
|
| 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. |
| Keywords: | Autophagy, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Lineage, Immunologic Memory, Inbred C57BL Mice, Knockout Mice, Mitochondria, Animals, Mice |
| Source: | Nature Cell Biology |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Volume: | 28 |
| Number: | 1 |
| Page Range: | 66-81 |
| Date: | January 2026 |
| Official Publication: | https://doi.org/10.1038/s41556-025-01835-2 |
| PubMed: | View item in PubMed |
| Related to: |
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