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Mitochondrial gene expression is required for platelet function and blood clotting

ABSTRACT: Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery which relies on nuclear encoded factors for the biogenesis of the oxidative phosphorylation (OXPHOS) system to produce energy, ions and metabolites required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is not known and platelets provide a valuable model to understand the importance of mitochondrial gene expression in anucleate cells. We generated three different platelet-specific conditional knockout mouse models, each lacking a gene that is essential for mitochondrial gene expression at the level of RNA processing, stability and translation (Elac2Pf4?/Pf4?, Ptcd1Pf4?/Pf4 and Mtif3Pf4?/Pf4?). Loss of ELAC2, PTCD1 or MTIF3, leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia and consequent extended bleeding time. Furthermore, impaired RNA metabolism also reduced agonist induced platelet activation. Transcriptomic and proteomic analyses showed that mitochondrial gene expression and protein synthesis facilitate fibrinolysis, haemostasis and blood coagulation in response to injury.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell, Blood

SUBMITTER: Stefan Siira

LAB HEAD: Aleksandra Filipovska

PROVIDER: PXD045688 | Pride | 2023-11-01

REPOSITORIES: Pride

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