ArticleEMBO molecular medicine2019
CoA-dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- CRISPR screening identifies DTX4 governing alveolar macrophage cholesterol efflux in pulmonary alveolar proteinosis.JCI insight · 2026Article
- Coenzyme A mitigates cystine-deprivation-induced ferroptosis by suppressing the iron-starvation response.The FEBS journal · 2026Article
- Mitochondrial phosphopantetheinylation is required for oxidative metabolism.Metabolism: clinical and experimental · 2026Article
- Coenzyme A in Brain Biology and Neurodegeneration.Biomedicines · 2025Review
- The mitochondrial trans-2-enoyl-CoA reductase is necessary for mitochondrial homeostasis in C. elegans.Genetics · 2025Article
- Boosting energy metabolism and biosynthesis in diverse organisms by a common bacterial salvage lipoylation protein.Nature communications · 2025Article
- NDUFAB1 as a Novel Regulator of NEFA-Induced Metabolic Dysfunction in Bovine Adipocytes.Animals : an open access journal from MDPI · 2025Article
- Characterization of the Pank2-/- mouse retinal phenotype as a pre-clinical model for pantothenate kinase-associated neurodegeneration.PloS one · 2025Article
- A therapeutic approach to pantothenate kinase associated neurodegeneration: a pilot study.Orphanet journal of rare diseases · 2024Article
- A Multi-Target Pharmacological Correction of a LipoyltransferaseAntioxidants (Basel, Switzerland) · 2024Article
- Emerging variants, unique phenotypes, and transcriptomic signatures: an integrated study of COASY-associated diseases.Annals of clinical and translational neurology · 2024Article
- Coenzyme A biosynthesis: mechanisms of regulation, function and disease.Nature metabolism · 2024Review
- The alpha-ketoacid dehydrogenase complexes ofmicroPublication biology · 2024Article
- Literature-based predictions of Mendelian disease therapies.American journal of human genetics · 2023Article
- Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2023Article
- Article
- Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments.International journal of molecular sciences · 2023Review
- Heterozygous Nonsense Variants in the Ferritin Heavy Chain GenemedRxiv : the preprint server for health sciences · 2023Article
- PPAR Gamma Agonist Leriglitazone Recovers Alterations Due to Pank2-Deficiency in hiPS-Derived Astrocytes.Pharmaceutics · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
PKAN, CoPAN, MePAN, and PDH-E2 deficiency share key phenotypic features but harbor defects in distinct metabolic processes. Selective damage to the globus pallidus occurs in these genetic neurodegenerative diseases, which arise from defects in CoA biosynthesis (PKAN, CoPAN), protein lipoylation (MePAN), and pyruvate dehydrogenase activity (PDH-E2 deficiency). Overlap of their clinical features suggests a common molecular etiology, the identification of which is required to understand their pathophysiology and design treatment strategies. We provide evidence that CoA-dependent activation of mitochondrial acyl carrier protein (mtACP) is a possible process linking these diseases through its effect on PDH activity. CoA is the source for the 4'-phosphopantetheine moiety required for the posttranslational 4'-phosphopantetheinylation needed to activate specific proteins. We show that impaired CoA homeostasis leads to decreased 4'-phosphopantetheinylation of mtACP. This results in a decrease of the active form of mtACP, and in turn a decrease in lipoylation with reduced activity of lipoylated proteins, including PDH. Defects in the steps of a linked CoA-mtACP-PDH pathway cause similar phenotypic abnormalities. By chemically and genetically re-activating PDH, these phenotypes can be rescued, suggesting possible treatment strategies for these diseases.
Indexed as
Identifiers
What 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.