Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0004134 (
ataxia
)
15,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans. 2244 45
