ArticlePLoS biology2012
Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 164 citations in OpenAlex.
- Tailored Amino Acid Treatment for Pediatric Patients With Mitochondrial Aminoacyl-tRNA Synthetase Deficiencies.Journal of inherited metabolic disease · 2026Article
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Genetics of Mitochondrial Aminoacyl-tRNA Synthetases Associated with Sensorineural Hearing Loss.Molecular syndromology · 2025Review
- A girl with intragenic variants inMolecular genetics and metabolism reports · 2025Article
- Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.Nucleic acids research · 2024Article
- Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.Frontiers in cell and developmental biology · 2024Review
- Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.Cell death discovery · 2023Article
- Bendless is essential for PINK1-Park mediated Mitofusin degradation under mitochondrial stress caused by loss of LRPPRC.PLoS genetics · 2023Article
- MARS1 mutations linked to familial trigeminal neuralgia via the integrated stress response.The journal of headache and pain · 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
- 'Fly-ing' from rare to common neurodegenerative disease mechanisms.Trends in genetics : TIG · 2022Review
- Novel phenotype and genotype spectrum of NARS2 and literature review of previous mutations.Irish journal of medical science · 2022Review
- Neuropathy-associated Fars2 deficiency affects neuronal development and potentiates neuronal apoptosis by impairing mitochondrial function.Cell & bioscience · 2022Article
- Aminoacyl-tRNA synthetases in human health and disease.Frontiers in physiology · 2022Review
- Autosomal recessive adult onset ataxia.Journal of neurology · 2022Article
- Mining massive genomic data of two Swiss Braunvieh cattle populations reveals six novel candidate variants that impair reproductive success.Genetics, selection, evolution : GSE · 2021Article
- FARS2 deficiency in Drosophila reveals the developmental delay and seizure manifested by aberrant mitochondrial tRNA metabolism.Nucleic acids research · 2021Article
- Roles of tRNA metabolism in aging and lifespan.Cell death & disease · 2021Review
- Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 9 institutions in 3 countries.
Funding
Abstract
An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues. We further observed that these mutants display defects in oxidative phosphorylation, increased Reactive Oxygen Species (ROS), and an upregulated mitochondrial Unfolded Protein Response. With the aid of this knowledge, we identified MARS2 to be mutated in Autosomal Recessive Spastic Ataxia with Leukoencephalopathy (ARSAL) patients. We uncovered complex rearrangements in the MARS2 gene in all ARSAL patients. Analysis of patient cells revealed decreased levels of MARS2 protein and a reduced rate of mitochondrial protein synthesis. Patient cells also exhibited reduced Complex I activity, increased ROS, and a slower cell proliferation rate, similar to Drosophila Aats-met mutants.
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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.