ArticleJournal of inherited metabolic disease2013
Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia.
Article in Journal of inherited metabolic disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Disturbances of Mitochondrial Functions and Oxidative Stress Induction in Methylmalonic and Propionic Acidemias: A Critical Role for Metabolite Accumulation.International journal of molecular sciences · 2026Review
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Mitochondrial Dysfunction in Propionic Acidemia: A Case-Report and Review of the Literature.JIMD reports · 2026Article
- Global Longitudinal Strain Alteration of the Left Ventricle in Children with Organic Aciduria: Cardiac Disease in Organic Aciduria.Journal of clinical medicine · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Transforming Growth Factor-β-Mediated Fibrotic Remodeling Drives Chronic Kidney Disease in Methylmalonic Aciduria and Propionic Aciduria-Identification of a New Therapeutic Target.Journal of inherited metabolic disease · 2025Article
- Metabolic flux analysis in hiPSC-CMs reveals insights into cardiac dysfunction in propionic acidemia.Cellular and molecular life sciences : CMLS · 2025Article
- Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.Scientific reports · 2024Article
- The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.Basic research in cardiology · 2024Article
- Neurodegenerative biomarkers and inflammation in patients with propionic and methylmalonic acidemias: effect of L-carnitine treatment.Metabolic brain disease · 2024Article
- Pathophysiological mechanisms of complications associated with propionic acidemia.Pharmacology & therapeutics · 2023Review
- Dietary Fiber Modulates the Release of Gut Bacterial Products Preventing Cognitive Decline in an Alzheimer's Mouse Model.Cellular and molecular neurobiology · 2023Article
- Review
- Plasma CoQ10 Status in Patients with Propionic Acidaemia and Possible Benefit of Treatment with Ubiquinol.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Case reports: three novel variants in PCCA and PCCB genes in Chinese patients with propionic acidemia.BMC medical genetics · 2020Article
- Cardiac Complications of Propionic and Other Inherited Organic Acidemias.Frontiers in cardiovascular medicine · 2020Review
- Carglumic Acid Contributes to a Favorable Clinical Course in a Case of Severe Propionic Acidemia.Case reports in pediatrics · 2020Article
- Neurological manifestations of organic acidurias.Nature reviews. Neurology · 2019Review
- Altered Redox Homeostasis in Branched-Chain Amino Acid Disorders, Organic Acidurias, and Homocystinuria.Oxidative medicine and cellular longevity · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. PA is caused by mutations in either the PCCA or PCCB genes encoding the α- and β-subunits of the PCC enzyme which are assembled as an α6β6 dodecamer. In this study we have investigated the molecular basis of the defect in ten fibroblast samples from PA patients. Using homology modeling with the recently solved crystal structure of the PCC holoenzyme and a eukaryotic expression system we have analyzed the structural and functional effect of novel point mutations, also revealing a novel splice defect by minigene analysis. In addition, we have investigated the contribution of oxidative stress to cellular damage measuring reactive oxygen species (ROS) levels and apoptosis parameters in patient fibroblasts, as recent studies point to a secondary mitochondrial dysfunction as pathophysiological mechanism in this disorder. The results show an increase in intracellular ROS content compared to controls, correlating with the activation of the JNK and p38 signaling pathways. Highest ROS levels were present in cells harboring functionally null mutations, including one severe missense mutation. This work provides molecular insight into the pathogenicity of PA variants and indicates that oxidative stress may be a major contributing factor to the cellular damage, supporting the proposal of antioxidant strategies as novel supplementary therapy in this rare disease.
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