ArticleJCI insight2023
Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- A scalable embryonic stem cell-based platform for efficient generation of mitochondrial DNA mutant mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-cell multi-omic analysis of mitochondrial mutational mosaicism and dynamics.Nature communications · 2026Article
- Immune Cell Mitochondrial Phenotypes Are Largely Preserved in Mitochondrial Diseases and Do Not Reflect Disease Severity.Neurology. Genetics · 2026Article
- Ubiquitous Expression ofLife (Basel, Switzerland) · 2025Article
- An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.Nature communications · 2025Article
- Tipping the balance: innate and adaptive immunity in mitochondrial disease.Current opinion in immunology · 2025Review
- Cell type-specific purifying selection of synonymous mitochondrial DNA variation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- T cell toxicity induced by tigecycline binding to the mitochondrial ribosome.Nature communications · 2025Article
- Disruption of adaptive immunity does not attenuate disease in the Ndufs4(-/-) model of Leigh syndrome.PloS one · 2025Article
- T cell activation contributes to purifying selection against the MELAS-associated m.3243A>G pathogenic variant in blood.Journal of inherited metabolic disease · 2024Article
- Mitochondrial genetics through the lens of single-cell multi-omics.Nature genetics · 2024Review
- Origins of tissue and cell-type specificity in mitochondrial DNA (mtDNA) disease.Human molecular genetics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. Pathogenic burden reduction was less pronounced in myeloid compared with lymphoid lineages, despite C5024T compromising macrophage OXPHOS capacity. Rapid dilution of the C5024T mutation in T and B cell cultures could be induced by antigen receptor-triggered proliferation and was accelerated by metabolic stress conditions. Furthermore, we found C5024T to dysregulate CD8+ T cell metabolic remodeling and IFN-γ production after activation. Together, our data illustrate that the generation of memory lymphocytes shapes the mtDNA landscape, wherein pathogenic variants dysregulate the immune response.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.