# The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function

## TL;DR

This paper shows that the choline transporter Slc44a2 affects platelet function and blood clotting by regulating mitochondrial energy production.

## Contribution

The study reveals a novel mechanism by which Slc44a2 influences thrombosis through mitochondrial choline metabolism and ATP production.

## Key findings

- Slc44a2 null mice have increased bleeding times and delayed thrombosis.
- Platelets lacking Slc44a2 show impaired activation and reduced ATP production.
- Exogenous ADP rescues the platelet activation defect in Slc44a2-deficient mice.

## 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.

Genetic association studies have identified loci including the choline transporter SLC44A2 as a potential regulator of thrombosis. Here the authors report that loss of SLC44A2 impairs platelet activation and thrombosis in mice via a reduction of mitochondrial ATP production.