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These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated. We show that HSP60 chaperone positively regulates the protein levels for multiple glutaminolysis- and FAO-related enzymes, thereby actively fueling the levels of cellular alpha-ketoglutarate (\u03b1KG) and related mitochondrial ATP-dependent antiviral T cell immunity in both CD4 and CD8 TM. Finally, we provide a way to rescue defective ATP generation in mitochondria and dependent effector functions in virus-specific TM including anti-HIV-1 protective responses, when HSP60 expression is impaired after TCR engagement in patients, in the form of dimethyl 2-oxoglutarate (DMKG) supplementation.<\/jats:p>","DOI":"10.1038\/s42003-024-07326-8","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T09:16:19Z","timestamp":1734772579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses"],"prefix":"10.1038","volume":"7","author":[{"given":"Nazanin","family":"Ghahari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saina","family":"Shegefti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Alaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amine","family":"Amara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Telittchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Isnard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Routy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-0674","authenticated-orcid":false,"given":"David","family":"Olagnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2952-4081","authenticated-orcid":false,"given":"Julien","family":"van Grevenynghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"7326_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2021.12.012","volume":"55","author":"NM Chapman","year":"2022","unstructured":"Chapman, N. 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