Protein Variants | Comment | Organism |
---|---|---|
additional information | the biochemical and molecular abnormalities in APTX-depleted cells are recapitulated by knockdown of APE1 in Hela cells and are rescued by overexpression of NRF1/2. Importantly, pharmacological upregulation of NRF1 alone by 5-aminoimidazone-4-carboxamide ribonucleotide does not rescue the phenotype, which, in contrast, is reversed by the upregulation of NRF2 by rosiglitazone. The lack of aprataxin causes reduction of the pathway APE1/NRF1/NRF2 and their target genes. APTX-mutant fibroblasts show reduced succinate dehydrogenase. APTX-mutant fibroblasts show reduced levels and biosynthesis of CoQ10. Levels of APE1 are reduced in APTX-mutant and APTX-depleted cells. Phenotype, overview | Homo sapiens |
W279X | naturally occuring mutation causing Ataxia oculomotor apraxia type 1 (AOA1) autosomal recessive disease | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q7Z2E3 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
fibroblast | - |
Homo sapiens | - |
HeLa cell | - |
Homo sapiens | - |
muscle | - |
Homo sapiens | - |
neuroblastoma cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
aprataxin | - |
Homo sapiens |
APTX | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | lack of aprataxin impairs mitochondrial functions, independent of its role in mitochondrial DNA repair, via downregulation of the APE1/NRF1/NRF2 pathway. Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency is identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized to mitochondria in neuroblastoma cells, where it enhances preservation of mitochondrial function. The bioenergetics defect in AOA1-mutant fibroblasts and APTX-depleted Hela cells is caused by decreased expression of SDHA and genes encoding CoQ biosynthetic enzymes, in association with reductions of APE1, NRF1 and NRF2. APE1 depletion impairs NRF1 expression in Hela cells and resembles APTX knockdown clones, mitochondrial genes are downregulated in APE1-deficient cells owing to the regulatory role of APE1 on DNA-binding and transcriptional activity of NRF1 | Homo sapiens |
physiological function | critical role of APTX in transcription regulation of mitochondrial function and the pathogenesis of AOA1 via a novel pathomechanistic pathway, which may be relevant to other neurodegenerative diseases | Homo sapiens |