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The fate of mitochondria during platelet activation

•Platelet mitochondria undergo a fission step during platelet activation.•The fission of platelet mitochondria correlates with a switch from a predominant mitochondrial to a more glycolytic energy production. [Display omitted] Blood platelets undergo several successive motor-driven reorganizations o...

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Published in:Blood advances 2023-10, Vol.7 (20), p.6290-6302
Main Authors: Grichine, Alexei, Jacob, Shancy, Eckly, Anita, Villaret, Joran, Joubert, Clotilde, Appaix, Florence, Pezet, Mylène, Ribba, Anne-Sophie, Denarier, Eric, Mazzega, Jacques, Rinckel, Jean-Yves, Lafanechère, Laurence, Elena-Herrmann, Bénédicte, Rowley, Jesse W., Sadoul, Karin
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Language:English
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Summary:•Platelet mitochondria undergo a fission step during platelet activation.•The fission of platelet mitochondria correlates with a switch from a predominant mitochondrial to a more glycolytic energy production. [Display omitted] Blood platelets undergo several successive motor-driven reorganizations of the cytoskeleton when they are recruited to an injured part of a vessel. These reorganizations take place during the platelet activation phase, the spreading process on the injured vessel or between fibrin fibers of the forming clot, and during clot retraction. All these steps require a lot of energy, especially the retraction of the clot when platelets develop strong forces similar to those of muscle cells. Platelets can produce energy through glycolysis and mitochondrial respiration. However, although resting platelets have only 5 to 8 individual mitochondria, they produce adenosine triphosphate predominantly via oxidative phosphorylation. Activated, spread platelets show an increase in size compared with resting platelets, and the question arises as to where the few mitochondria are located in these larger platelets. Using expansion microscopy, we show that the number of mitochondria per platelet is increased in spread platelets. Live imaging and focused ion beam–scanning electron microscopy suggest that a mitochondrial fission event takes place during platelet activation. Fission is Drp1 dependent because Drp1-deficient platelets have fused mitochondria. In nucleated cells, mitochondrial fission is associated with a shift to a glycolytic phenotype, and using clot retraction assays, we show that platelets have a more glycolytic energy production during clot retraction and that Drp1-deficient platelets show a defect in clot retraction.
ISSN:2473-9529
2473-9537
2473-9537
DOI:10.1182/bloodadvances.2023010423