ReferenceID 4080
The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function
Nat Commun
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 plate
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Record Fields
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- Reference Id
- 4080
- Evidence Id
- 20670
- Core Evidence Id
- 20670
- Source Reference Id
- 3039
- Herb2 Reference Id
- HBREF003836
- Subject Paper Key
- HBIN020406_32661250
- Pubmed Id
- 32661250
- Doi
- 10.1038/s41467-020-17254-w
- Paper Title
- The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function
- Paper 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.
- Journal
- Nat Commun
- Publish Year
- 2020
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Thrombosis; Delayed Thrombosis; Thrombotic Diseases
- Paper Title Cn
- Paper Title En
- The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function
- Bilingual Status
- semi_complete