ArticleInternational journal of molecular sciences2022
VARS2 Depletion Leads to Activation of the Integrated Stress Response and Disruptions in Mitochondrial Fatty Acid Oxidation.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- IBAS: Interaction-bridged association studies discovering novel genes underlying complex traits.PLoS computational biology · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- Article
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- Genes Encoding Heat Shock Proteins Are Associated with Risk and Clinical Course of Severe COVID-19: A Pilot Study.International journal of molecular sciences · 2025Article
- Novel Variants in VARS2 Demonstrate the Phenotypic Variability of a Rare Mitochondriopathy That Responds to Valine Supplementation.Journal of inherited metabolic disease · 2025Article
- Exploring the Associated Genetic Causes of Diabetic Retinopathy as a Model of Inflammation in Retinal Diseases.International journal of molecular sciences · 2024Article
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in mitochondrial aminoacyl-tRNA synthetases (mtARSs) have been reported in patients with mitochondriopathies: most commonly encephalopathy, but also cardiomyopathy. Through a GWAS, we showed possible associations between mitochondrial valyl-tRNA synthetase (VARS2) dysregulations and non-ischemic cardiomyopathy. We aimed to investigate the possible consequences of VARS2 depletion in zebrafish and cultured HEK293A cells. Transient VARS2 loss-of-function was induced in zebrafish embryos using Morpholinos. The enzymatic activity of VARS2 was measured in VARS2-depleted cells via northern blot. Heterozygous VARS2 knockout was established in HEK293A cells using CRISPR/Cas9 technology. BN-PAGE and SDS-PAGE were used to investigate electron transport chain (ETC) complexes, and the oxygen consumption rate and extracellular acidification rate were measured using a Seahorse XFe96 Analyzer. The activation of the integrated stress response (ISR) and possible disruptions in mitochondrial fatty acid oxidation (FAO) were explored using RT-qPCR and western blot. Zebrafish embryos with transient VARS2 loss-of-function showed features of heart failure as well as indications of CNS and skeletal muscle involvements. The enzymatic activity of VARS2 was significantly reduced in VARS2-depleted cells. Heterozygous VARS2-knockout cells showed a rearrangement of ETC complexes in favor of complexes III
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