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Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation

Slatter, David A., Aldrovandi, Maceler, O'Connor, Anne ORCID:, Allen, Stuart M., Brasher, Christopher J., Murphy, Robert C., Mecklemann, Sven, Ravi, Saranya, Darley-Usmar, Victor and O'Donnell, Valerie B. ORCID: 2016. Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation. Cell Metabolism 23 (5) , pp. 930-944. 10.1016/j.cmet.2016.04.001

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Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via β-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QH Natural history > QH426 Genetics
Additional Information: This article is available under a Creative Commons License
Publisher: Elsevier
ISSN: 1550-4131
Funders: Wellcome Trust
Date of First Compliant Deposit: 6 April 2016
Date of Acceptance: 31 March 2016
Last Modified: 13 May 2023 17:31

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