ArticleAmerican journal of human genetics1995
An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein.
Article in American journal of human genetics, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 48 citations in OpenAlex.
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
- TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease.Nature communications · 2023Article
- Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy.Human mutation · 2022Article
- Solvent accessibility of E1α and E1β residues with known missense mutations causing pyruvate dehydrogenase complex (PDC) deficiency: Impact on PDC-E1 structure and function.Journal of inherited metabolic disease · 2022Article
- Disease-Associated Genetic Variation in Human Mitochondrial Protein Import.American journal of human genetics · 2019Review
- Mitochondrial proteins: from biogenesis to functional networks.Nature reviews. Molecular cell biology · 2019Review
- Utilizing Optimized Tools to Investigate PTM Crosstalk: Identifying Potential PTM Crosstalk of Acetylated Mitochondrial Proteins.Proteomes · 2018Article
- Heterogeneity in Cancer Metabolism: New Concepts in an Old Field.Antioxidants & redox signaling · 2017Review
- MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites.Molecular & cellular proteomics : MCP · 2015Article
- Health risks of space exploration: targeted and nontargeted oxidative injury by high-charge and high-energy particles.Antioxidants & redox signaling · 2014Review
- Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury.Cancer letters · 2012Review
- The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.Molecular genetics and metabolism · 2012Article
- The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients.Molecular genetics and metabolism · 2012Review
- Mitochondrial targeting of human NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2) and its association with early-onset hypertrophic cardiomyopathy and encephalopathy.Journal of biomedical science · 2011Article
- A history of mitochondrial diseases.Journal of inherited metabolic disease · 2011Article
- Historical perspective on mitochondrial medicine.Developmental disabilities research reviews · 2010Article
- Mitochondrial biogenesis and turnover.Cell calcium · 2008Review
- Mitochondrial protein import and human health and disease.Biochimica et biophysica acta · 2007Review
- Mitochondrial encephalomyopathies: what next?Journal of inherited metabolic disease · 1996Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A mutation in the mitochondrial targeting sequence was characterized in a male patient with X chromosome-linked pyruvate dehydrogenase E1 alpha deficiency. The mutation was a base substitution of G by C at nucleotide 134 in the mitochondrial targeting sequence of the PDHA1 gene, resulting in an arginine-to-proline substitution at codon 10 (R10P). Pyruvate dehydrogenase activity in cultured skin fibroblasts was 28% of the control value, and immunoblot analysis revealed a decreased level of pyruvate dehydrogenase E1 alpha immunoreactivity. Chimeric constructs in which the normal and mutant pyruvate dehydrogenase E1 alpha targeting sequences were attached to the mitochondrial matrix protein ornithine transcarbamylase were synthesized in a cell free translation system, and mitochondrial import of normal and mutant proteins was compared in vitro. The results show that ornithine transcarbamylase targeted by the mutant pyruvate dehydrogenase E1 alpha sequence was translocated into the mitochondrial matrix at a reduced rate, suggesting that defective import is responsible for the reduced pyruvate dehydrogenase level in mitochondria. The mutation was also present in an affected brother and the mildly affected mother. The clinical presentations of this X chromosome-linked disorder in affected family members are discussed. To our knowledge, this is the first report of an amino acid substitution in a mitochondrial targeting sequence resulting in a human genetic disease.
Indexed as
Identifiers
7573035PMC1801496W1607985964What OpenQuestion holds
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.