Jingdian Zhang, Camilla Koolmeister, Jinming Han, Roberta Filograna, Leo Hanke, Monika Àdori, Daniel J Sheward, Sina Teifel, Shreekara Gopalakrishna, Qiuya Shao, Yong Liu, Keying Zhu, Robert A Harris, Gerald McInerney, Ben Murrell, Mike Aoun, Liselotte Bäckdahl, Rikard Holmdahl, Marcin Pekalski, Anna Wedell, Martin Engvall, Anna Wredenberg, Gunilla B Karlsson Hedestam, Xaquin Castro Dopico, Joanna Rorbach
Pathogenic mutations in mitochondrial (mt) tRNA genes that compromise oxidative phosphorylation (OXPHOS) exhibit heteroplasmy and cause a range of multisyndromic conditions. Although mitochondrial disease patients are known to suffer from abnormal immune responses, how heteroplasmic mtDNA mutations affect the immune system at the molecular level is largely unknown. Here, in mice carrying pathogenic C5024T in mt-tRNAAla and in patients with mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) syndrome carrying A3243G in mt-tRNALeu, we found memory T and B cells to have lower pathogenic mtDNA mutation burdens than their antigen-inexperienced naive counterparts, including after vaccination...
September 8, 2023: JCI Insight