| First Author | Yang JF | Year | 2023 |
| Journal | Sci Immunol | Volume | 8 |
| Issue | 87 | Pages | eabq2424 |
| PubMed ID | 37738362 | Mgi Jnum | J:350207 |
| Mgi Id | MGI:7661184 | Doi | 10.1126/sciimmunol.abq2424 |
| Citation | Yang JF, et al. (2023) Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8(+) T cell metabolic fitness and function in tumors. Sci Immunol 8(87):eabq2424 |
| abstractText | Metabolic fitness of T cells is essential for their vitality, which is largely dependent on the behavior of the mitochondria. The nature of mitochondrial behavior in tumor-infiltrating T cells remains poorly understood. In this study, we show that mitofusin-2 (MFN2) expression is positively correlated with the prognosis of multiple cancers. Genetic ablation of Mfn2 in CD8(+) T cells dampens mitochondrial metabolism and function and promotes tumor progression. In tumor-infiltrating CD8(+) T cells, MFN2 enhances mitochondria-endoplasmic reticulum (ER) contact by interacting with ER-embedded Ca(2+)-ATPase SERCA2, facilitating the mitochondrial Ca(2+) influx required for efficient mitochondrial metabolism. MFN2 stimulates the ER Ca(2+) retrieval activity of SERCA2, thereby preventing excessive mitochondrial Ca(2+) accumulation and apoptosis. Elevating mitochondria-ER contact by increasing MFN2 in CD8(+) T cells improves the efficacy of cancer immunotherapy. Thus, we reveal a tethering-and-buffering mechanism of organelle cross-talk that regulates the metabolic fitness of tumor-infiltrating CD8(+) T cells and highlights the therapeutic potential of enhancing MFN2 expression to optimize T cell function. |
