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: https://orcid.org/0000-0003-2268-4231, Allen, Stuart M., Brasher, Christopher J., Murphy, Robert C., Mecklemann, Sven, Ravi, Saranya, Darley-Usmar, Victor and O'Donnell, Valerie B. ORCID: https://orcid.org/0000-0003-4089-8460 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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Abstract

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
URI:	https://orca.cardiff.ac.uk/id/eprint/88691

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