ArticleNature chemical biology2015
Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis.
Article in Nature chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 128 citations in OpenAlex.
- Supplementation via DAF-16 andbioRxiv : the preprint server for biology · 2026Article
- Therapeutic Advances in Major NBIA Disorders: Current Strategies and Translational Challenges.Neurology international · 2026Review
- Energetic stress in combination with impaired fatty acid oxidation induces sequestration of CoA and adaptation of CoA metabolism.The FEBS journal · 2026Article
- MESH1-mediated coenzyme A degradation drives ferroptosis sensitivity and muscle pathology.The Journal of clinical investigation · 2026Article
- Coenzyme A mitigates cystine-deprivation-induced ferroptosis by suppressing the iron-starvation response.The FEBS journal · 2026Article
- Renal coenzyme A (CoA) production from VB5 fuels stem cell proliferation and tumor growth.Nature communications · 2026Article
- Mitigating the impact of study-start delays in clinical trials for rare disorders: insights and lessons from a PKAN trial.Orphanet journal of rare diseases · 2025Article
- Article
- Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.The Journal of clinical investigation · 2025Article
- Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation.Nature communications · 2025Article
- Pantethine therapy dramatically rescues end-stage failing heart in a patient with deficiency of coenzyme A biosynthesis.ESC heart failure · 2025Article
- ACSS2-Mediated Histone H4 Lysine 12 Crotonylation (H4K12cr) Alleviates Colitis via Enhancing Transcription of CLDN7.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pantethine ameliorates dilated cardiomyopathy features in PPCS deficiency disorder in patients and cell line models.Communications medicine · 2025Article
- HLH-30/TFEB Rewires the Chaperone Network to Promote Proteostasis Upon Perturbations to the Coenzyme A and Iron-Sulfur Cluster Biosynthesis Pathways.Aging cell · 2025Article
- Dietary sulfur amino acid restriction improves metabolic health by reducing fat mass.Life metabolism · 2025Article
- iPSC-Derived Liver Organoids as a Tool to Study Medium Chain Acyl-CoA Dehydrogenase Deficiency.Journal of inherited metabolic disease · 2025Article
- Feedforward cysteine regulation maintains melanoma differentiation state and limits metastatic spread.Cell reports · 2024Article
- Coenzyme A biosynthesis: mechanisms of regulation, function and disease.Nature metabolism · 2024Review
- Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis.PLoS pathogens · 2023Article
- Starving the Beast: Limiting Coenzyme A Biosynthesis to Prevent Disease and Transmission in Malaria.International journal of molecular sciences · 2023Review
16 more citing papers are in PubMed but not listed here.
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16 authors at 4 institutions in 3 countries.
Funding
Abstract
The metabolic cofactor coenzyme A (CoA) gained renewed attention because of its roles in neurodegeneration, protein acetylation, autophagy and signal transduction. The long-standing dogma is that eukaryotic cells obtain CoA exclusively via the uptake of extracellular precursors, especially vitamin B5, which is intracellularly converted through five conserved enzymatic reactions into CoA. This study demonstrates an alternative mechanism that allows cells and organisms to adjust intracellular CoA levels by using exogenous CoA. Here CoA was hydrolyzed extracellularly by ectonucleotide pyrophosphatases to 4'-phosphopantetheine, a biologically stable molecule able to translocate through membranes via passive diffusion. Inside the cell, 4'-phosphopantetheine was enzymatically converted back to CoA by the bifunctional enzyme CoA synthase. Phenotypes induced by intracellular CoA deprivation were reversed when exogenous CoA was provided. Our findings answer long-standing questions in fundamental cell biology and have major implications for the understanding of CoA-related diseases and therapies.
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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.