ArticleHuman molecular genetics2011
Altered zinc transport disrupts mitochondrial protein processing/import in fragile X-associated tremor/ataxia syndrome.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 107 citations in OpenAlex.
- Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study.Molecular neurobiology · 2019Trial
- Memantine for fragile X-associated tremor/ataxia syndrome: a randomized, double-blind, placebo-controlled trial.The Journal of clinical psychiatry · 2014Trial
- Mitochondrial degradation of metallothionein enables local zinc mobilization during zinc limitation.bioRxiv : the preprint server for biology · 2026Article
- Progression of fragile X-associated tremor/ataxia syndrome revealed by subtype and stage inference.Brain communications · 2026Article
- Loss of Fmr1 reorganizes the multi-elemental composition across tissues in Fragile X Syndrome mice.PloS one · 2026Article
- Fragile X Syndrome and FMR1 premutation: results from a survey on associated conditions and treatment priorities in Italy.Orphanet journal of rare diseases · 2024Article
- Mitochondrial dysfunction in brain tissues and Extracellular Vesicles Fragile X-associated tremor/ataxia syndrome.Annals of clinical and translational neurology · 2024Article
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases.Epigenomics · 2024Review
- Mitochondrial Dysfunction Causes Cell Death in Patients Affected by Fragile-X-Associated Disorders.International journal of molecular sciences · 2024Article
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- Article
- Review
- Clinical implications of somatic allele expansion in female FMR1 premutation carriers.Scientific reports · 2023Article
- Fragile X-Associated Neuropsychiatric Disorders (FXAND) in Young Fragile X Premutation Carriers.Genes · 2022Article
- Artificial neural network applied to fragile X-associated tremor/ataxia syndrome stage diagnosis based on peripheral mitochondrial bioenergetics and brain imaging outcomes.Scientific reports · 2022Article
- Autism spectrum disorder in the fragile X premutation state: possible mechanisms and implications.Journal of neurology · 2022Review
- Review
- Neurodegenerative diseases associated with non-coding CGG tandem repeat expansions.Nature reviews. Neurology · 2022Review
- Clinical and Molecular Correlates of Abnormal Changes in the Cerebellum and Globus Pallidus in Fragile X Premutation.Frontiers in neurology · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects individuals who are carriers of small CGG premutation expansions in the fragile X mental retardation 1 (FMR1) gene. Mitochondrial dysfunction was observed as an incipient pathological process occurring in individuals who do not display overt features of FXTAS (1). Fibroblasts from premutation carriers had lower oxidative phosphorylation capacity (35% of controls) and Complex IV activity (45%), and higher precursor-to-mature ratios (P:M) of nDNA-encoded mitochondrial proteins (3.1-fold). However, fibroblasts from carriers with FXTAS symptoms presented higher FMR1 mRNA expression (3-fold) and lower Complex V (38%) and aconitase activities (43%). Higher P:M of ATPase β-subunit (ATPB) and frataxin were also observed in cortex from patients that died with FXTAS symptoms. Biochemical findings observed in FXTAS cells (lower mature frataxin, lower Complex IV and aconitase activities) along with common phenotypic traits shared by Friedreich's ataxia and FXTAS carriers (e.g. gait ataxia, loss of coordination) are consistent with a defective iron homeostasis in both diseases. Higher P:M, and lower ZnT6 and mature frataxin protein expression suggested defective zinc and iron metabolism arising from altered ZnT protein expression, which in turn impairs the activity of mitochondrial Zn-dependent proteases, critical for the import and processing of cytosolic precursors, such as frataxin. In support of this hypothesis, Zn-treated fibroblasts showed a significant recovery of ATPB P:M, ATPase activity and doubling time, whereas Zn and desferrioxamine extended these recoveries and rescued Complex IV activity.
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