ArticleNature communications2020
The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Predictive value of neutrophil to lymphocyte ratio for clinical outcome in patients with atrial fibrillation: a systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2024Pooled it
- Machine learning-based prognostic signature integrating mitochondrial function and programmed cell death patterns in pancreatic adenocarcinoma.Scientific reports · 2026Article
- Super-Enhancer-Driven SOX4/SMAD3 Mediate Membrane Remodeling by Regulating Phospholipid Metabolism to Accelerate Leukemia Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of repeated 14-day oral toxicity of fermentedOpen veterinary journal · 2025Article
- Genetic factors for hematological traits in pigs.Animal genetics · 2025Review
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- SLC44A2 negatively regulates mitochondrial fatty acid oxidation to suppress colorectal progression by blocking the MUL1-CPT2 interaction.Cell death & disease · 2025Article
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Role of von Willebrand factor (VWF), platelets, and aberrant flow in the initiation of venous thrombosis.Science advances · 2025Article
- A data-mining analysis of host solute carrier family proteins in SARS-CoV-2 infection with reference to brain endothelial cells and the blood-brain barrier in COVID-19.Frontiers in neurology · 2025Article
- RNAi screens identify HES4 as a regulator of redox balance supporting pyrimidine synthesis and tumor growth.Nature structural & molecular biology · 2024Article
- Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024Review
- SLC44A2-mediated phenotypic switch of vascular smooth muscle cells contributes to aortic aneurysm.The Journal of clinical investigation · 2024Article
- The proteomic landscape of in vitro cultured endothelial cells across vascular beds.Communications biology · 2024Article
- Generation and characterisation of scalable and stable human pluripotent stem cell-derived microvascular-like endothelial cells for cardiac applications.Angiogenesis · 2024Article
- SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm.The Journal of clinical investigation · 2024Article
- The Effects ofAnimals : an open access journal from MDPI · 2024Article
- Identification of candidate regulatory genes for intramuscular fatty acid composition in pigs by transcriptome analysis.Genetics, selection, evolution : GSE · 2024Article
- GENETIC DETERMINANTS OF THROMBOSIS.Transactions of the American Clinical and Climatological Association · 2024Article
- Chronic Thromboembolic Pulmonary Hypertension: A Review of the Multifaceted Pathobiology.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis.
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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.