Mitochondria regulate MR1 protein expression and produce self-metabolites that activate MR1-restricted T cells.

ABSTRACT: Mitochondria coordinate several metabolic pathways, producing metabolites that influence the immune response in various ways. It remains unclear whether mitochondria impact antigen presentation by the MHC-class-I-related antigen-presenting molecule, MR1, which presents small molecules to MR1-restricted T-lymphocytes. Here, we demonstrate that mitochondrial complex III and the enzyme dihydroorotate dehydrogenase are essential for the cell-surface expression of MR1 and for generating uridine- and thymidine-related compounds that bind to MR1 and are produced upon oxidation by reactive oxygen species. One mitochondria-derived immunogenic formylated metabolite we identified is 5-formyl-deoxyuridine (5-FdU). Structural studies indicate that 5-FdU binds in the A'-antigen-binding pocket of MR1, po

SUBMITTER: Prota G 

PROVIDER: S-EPMC12107159 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature