Travis Nemkov, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Alicia Key, Zachary B. Haiman, Christopher Erickson, Monika Dzieciatkowska, Julie A. Reisz, Amy Moore, Mars Stone, Xutao Deng, Steven Kleinman, Steven L. Spitalnik, Eldad A. Hod, Krystalyn E. Hudson, Kirk C. Hansen, Bernhard O. Palsson, Gary A. Churchill, Angelo D’Alessandro
{"title":"Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes","authors":"Travis Nemkov, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Alicia Key, Zachary B. Haiman, Christopher Erickson, Monika Dzieciatkowska, Julie A. Reisz, Amy Moore, Mars Stone, Xutao Deng, Steven Kleinman, Steven L. Spitalnik, Eldad A. Hod, Krystalyn E. Hudson, Kirk C. Hansen, Bernhard O. Palsson, Gary A. Churchill, Angelo D’Alessandro","doi":"10.1016/j.cmet.2024.06.007","DOIUrl":null,"url":null,"abstract":"<p>Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging <em>in vivo</em> or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage. ATP and hypoxanthine (HYPX) levels—and the genetic traits linked to them—were associated with hemolysis <em>in vitro</em> and <em>in vivo</em>, both in healthy autologous transfusion recipients and in 5,816 critically ill patients receiving heterologous transfusions, suggesting their potential as markers to improve transfusion outcomes.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"93 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2024.06.007","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage. ATP and hypoxanthine (HYPX) levels—and the genetic traits linked to them—were associated with hemolysis in vitro and in vivo, both in healthy autologous transfusion recipients and in 5,816 critically ill patients receiving heterologous transfusions, suggesting their potential as markers to improve transfusion outcomes.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.