{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:30:15Z","timestamp":1792114215496,"version":"4.4.0"},"reference-count":141,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gansu Science and Technology Project of China","award":["23JRRA1100"],"award-info":[{"award-number":["23JRRA1100"]}]},{"name":"Gansu Science and Technology Project of China","award":["82001675"],"award-info":[{"award-number":["82001675"]}]},{"name":"Gansu Science and Technology Project of China","award":["82272342"],"award-info":[{"award-number":["82272342"]}]},{"name":"Gansu Science and Technology Project of China","award":["lzujbky-2023-17"],"award-info":[{"award-number":["lzujbky-2023-17"]}]},{"name":"the National Natural Science Foundation of China","award":["23JRRA1100"],"award-info":[{"award-number":["23JRRA1100"]}]},{"name":"the National Natural Science Foundation of China","award":["82001675"],"award-info":[{"award-number":["82001675"]}]},{"name":"the National Natural Science Foundation of China","award":["82272342"],"award-info":[{"award-number":["82272342"]}]},{"name":"the National Natural Science Foundation of China","award":["lzujbky-2023-17"],"award-info":[{"award-number":["lzujbky-2023-17"]}]},{"name":"Fundamental Research Funds for the Central Universities of Lanzhou University","award":["23JRRA1100"],"award-info":[{"award-number":["23JRRA1100"]}]},{"name":"Fundamental Research Funds for the Central Universities of Lanzhou University","award":["82001675"],"award-info":[{"award-number":["82001675"]}]},{"name":"Fundamental Research Funds for the Central Universities of Lanzhou University","award":["82272342"],"award-info":[{"award-number":["82272342"]}]},{"name":"Fundamental Research Funds for the Central Universities of Lanzhou University","award":["lzujbky-2023-17"],"award-info":[{"award-number":["lzujbky-2023-17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>T cells play a vital role in resisting pathogen invasion and maintaining immune homeostasis. However, T cells gradually become exhausted under chronic antigenic stimulation, and this exhaustion is closely related to mitochondrial dysfunction in T cells. Mitochondria play a crucial role in the metabolic reprogramming of T cells to achieve the desired immune response. Here, we compiled the latest research on how mitochondrial metabolism determines T cell function and differentiation, with the mechanisms mainly including mitochondrial biogenesis, fission, fusion, mitophagy, and mitochondrial transfer. In addition, the alterations in mitochondrial metabolism in T-cell exhaustion were also reviewed. Furthermore, we discussed intervention strategies targeting mitochondrial metabolism to reverse T cell exhaustion in detail, including inducing PGC-1\u03b1 expression, alleviating reactive oxygen species (ROS) production or hypoxia, enhancing ATP production, and utilizing mitochondrial transfer. Targeting mitochondrial metabolism in exhausted T cells may achieve the goal of reversing and preventing T cell exhaustion.<\/jats:p>","DOI":"10.3390\/ijms26157400","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Mitochondrial Metabolism in T-Cell Exhaustion"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4251-4291","authenticated-orcid":false,"given":"Fei","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zesheng","family":"Yin","sequence":"additional","affiliation":[{"name":"Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. 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