Mitochondrial gene expression is required for platelet function and blood clotting
Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for t...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | http://purl.org/au-research/grants/arc/DP180101656 http://hdl.handle.net/20.500.11937/94737 |
| _version_ | 1848765909592702976 |
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| author | Richman, T.R. Ermer, J.A. Baker, J. Siira, S.J. Kile, B.T. Linden, M.D. Rackham, Oliver Filipovska, A. |
| author_facet | Richman, T.R. Ermer, J.A. Baker, J. Siira, S.J. Kile, B.T. Linden, M.D. Rackham, Oliver Filipovska, A. |
| author_sort | Richman, T.R. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is unclear, and platelets provide a valuable model to understand its importance in anucleate cells. Here, we conditionally delete Elac2, Ptcd1, or Mtif3 in platelets, which are essential for mitochondrial gene expression at the level of RNA processing, stability, or translation, respectively. Loss of ELAC2, PTCD1, or MTIF3 leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia, and consequent extended bleeding time. Impaired mitochondrial gene expression reduces agonist-induced platelet activation. Transcriptomic and proteomic analyses show that mitochondrial gene expression is required for fibrinolysis, hemostasis, and blood coagulation in response to injury. |
| first_indexed | 2025-11-14T11:42:44Z |
| format | Journal Article |
| id | curtin-20.500.11937-94737 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:42:44Z |
| publishDate | 2023 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-947372024-05-07T08:06:13Z Mitochondrial gene expression is required for platelet function and blood clotting Richman, T.R. Ermer, J.A. Baker, J. Siira, S.J. Kile, B.T. Linden, M.D. Rackham, Oliver Filipovska, A. CP: Immunology megakaryocytes mitochondria mitochondrial gene expression platelets translation Humans Genes, Mitochondrial Proteomics Hemostasis Blood Coagulation Blood Platelets Megakaryocytes Thrombosis Gene Expression Mitochondrial Proteins Blood Platelets Megakaryocytes Humans Thrombosis Mitochondrial Proteins Proteomics Gene Expression Hemostasis Blood Coagulation Genes, Mitochondrial Platelets are anucleate blood cells that contain mitochondria and regulate blood clotting in response to injury. Mitochondria contain their own gene expression machinery that relies on nuclear-encoded factors for the biogenesis of the oxidative phosphorylation system to produce energy required for thrombosis. The autonomy of the mitochondrial gene expression machinery from the nucleus is unclear, and platelets provide a valuable model to understand its importance in anucleate cells. Here, we conditionally delete Elac2, Ptcd1, or Mtif3 in platelets, which are essential for mitochondrial gene expression at the level of RNA processing, stability, or translation, respectively. Loss of ELAC2, PTCD1, or MTIF3 leads to increased megakaryocyte ploidy, elevated circulating levels of reticulated platelets, thrombocytopenia, and consequent extended bleeding time. Impaired mitochondrial gene expression reduces agonist-induced platelet activation. Transcriptomic and proteomic analyses show that mitochondrial gene expression is required for fibrinolysis, hemostasis, and blood coagulation in response to injury. 2023 Journal Article http://hdl.handle.net/20.500.11937/94737 10.1016/j.celrep.2023.113312 eng http://purl.org/au-research/grants/arc/DP180101656 http://creativecommons.org/licenses/by-nc-nd/4.0/ fulltext |
| spellingShingle | CP: Immunology megakaryocytes mitochondria mitochondrial gene expression platelets translation Humans Genes, Mitochondrial Proteomics Hemostasis Blood Coagulation Blood Platelets Megakaryocytes Thrombosis Gene Expression Mitochondrial Proteins Blood Platelets Megakaryocytes Humans Thrombosis Mitochondrial Proteins Proteomics Gene Expression Hemostasis Blood Coagulation Genes, Mitochondrial Richman, T.R. Ermer, J.A. Baker, J. Siira, S.J. Kile, B.T. Linden, M.D. Rackham, Oliver Filipovska, A. Mitochondrial gene expression is required for platelet function and blood clotting |
| title | Mitochondrial gene expression is required for platelet function and blood clotting |
| title_full | Mitochondrial gene expression is required for platelet function and blood clotting |
| title_fullStr | Mitochondrial gene expression is required for platelet function and blood clotting |
| title_full_unstemmed | Mitochondrial gene expression is required for platelet function and blood clotting |
| title_short | Mitochondrial gene expression is required for platelet function and blood clotting |
| title_sort | mitochondrial gene expression is required for platelet function and blood clotting |
| topic | CP: Immunology megakaryocytes mitochondria mitochondrial gene expression platelets translation Humans Genes, Mitochondrial Proteomics Hemostasis Blood Coagulation Blood Platelets Megakaryocytes Thrombosis Gene Expression Mitochondrial Proteins Blood Platelets Megakaryocytes Humans Thrombosis Mitochondrial Proteins Proteomics Gene Expression Hemostasis Blood Coagulation Genes, Mitochondrial |
| url | http://purl.org/au-research/grants/arc/DP180101656 http://hdl.handle.net/20.500.11937/94737 |