ArticleCell reports2018
A Wars2 Mutant Mouse Model Displays OXPHOS Deficiencies and Activation of Tissue-Specific Stress Response Pathways.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Multiple mechanisms lead to loss-of-function effects of pathogenic SARS2 variants.Disease models & mechanisms · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- tRNA synthetase activity is required for stress granule and P-body assembly.Genes & development · 2026Article
- The Role and Research Progress of Mitochondria in Sensorineural Hearing Loss.Molecular neurobiology · 2025Review
- Mitochondrial damage in muscle specific PolG mutant mice activates the integrated stress response and disrupts the mitochondrial folate cycle.Nature communications · 2025Article
- Disentangling the genetic overlap between ischemic stroke and obesity.Diabetology & metabolic syndrome · 2024Article
- A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants.HGG advances · 2024Article
- Illuminating mitochondrial translation through mouse models.Human molecular genetics · 2024Review
- FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System.Circulation · 2024Article
- Predictive biomarkers for the early detection and management of heart failure.Heart failure reviews · 2024Review
- The genetics of adipose tissue metabolism.Royal Society open science · 2024Article
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
- Mtfp1 ablation enhances mitochondrial respiration and protects against hepatic steatosis.Nature communications · 2023Article
- FAM210A regulates mitochondrial translation and maintains cardiac mitochondrial homeostasis.Cardiovascular research · 2023Article
- Mutations in DARS2 result in global dysregulation of mRNA metabolism and splicing.Scientific reports · 2023Article
- Mutations in DARS2 result in global dysregulation of mRNA metabolism and splicing.Research square · 2023Article
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease.Genes · 2022Review
- VARS2 Depletion Leads to Activation of the Integrated Stress Response and Disruptions in Mitochondrial Fatty Acid Oxidation.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in genes essential for mitochondrial function have pleiotropic effects. The mechanisms underlying these traits yield insights into metabolic homeostasis and potential therapies. Here we report the characterization of a mouse model harboring a mutation in the tryptophanyl-tRNA synthetase 2 (Wars2) gene, encoding the mitochondrial-localized WARS2 protein. This hypomorphic allele causes progressive tissue-specific pathologies, including hearing loss, reduced adiposity, adipose tissue dysfunction, and hypertrophic cardiomyopathy. We demonstrate the tissue heterogeneity arises as a result of variable activation of the integrated stress response (ISR) pathway and the ability of certain tissues to respond to impaired mitochondrial translation. Many of the systemic metabolic effects are likely mediated through elevated fibroblast growth factor 21 (FGF21) following activation of the ISR in certain tissues. These findings demonstrate the potential pleiotropy associated with Wars2 mutations in patients.
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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.