Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes.

Autor:	Nemkov T; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies Inc., Aurora, CO, USA., Stephenson D; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA., Earley EJ; RTI International, Atlanta, GA, USA., Keele GR; Jackson Laboratory, Bar Harbor, ME, USA., Hay A; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Key A; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA., Haiman ZB; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Erickson C; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA., Dzieciatkowska M; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA., Reisz JA; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA., Moore A; RTI International, Atlanta, GA, USA., Stone M; Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA., Deng X; Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA., Kleinman S; University of British Columbia, Victoria, BC, Canada., Spitalnik SL; Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Hod EA; Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Hudson KE; Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York, NY, USA., Hansen KC; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies Inc., Aurora, CO, USA., Palsson BO; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA., Churchill GA; Jackson Laboratory, Bar Harbor, ME, USA., Roubinian N; Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA; Kaiser Permanente Northern California Division of Research, Oakland, CA, USA., Norris PJ; Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA., Busch MP; Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA., Zimring JC; Department of Pathology, University of Virginia, Charlottesville, VA, USA., Page GP; RTI International, Atlanta, GA, USA., D'Alessandro A; Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies Inc., Aurora, CO, USA. Electronic address: angelo.dalessandro@cuanschutz.edu.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2024 Sep 03; Vol. 36 (9), pp. 1979-1997.e13. Date of Electronic Publication: 2024 Jul 03.
DOI:	10.1016/j.cmet.2024.06.007
Abstrakt:	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. Competing Interests: Declaration of interests A.D’A., K.C.H., and T.N. are founders of Omix Technologies Inc. and Altis Biosciences LLC. A.D’A., S.L.S., and T.N. are Scientific Advisory Board (SAB) members for Hemanext Inc. A.D’A. is an SAB member for Macopharma Inc. S.L.S. is an SAB member for Alcor, Inc.; a consultant for Team Conveyer Intellectual Properties; executive director for Worldwide Initiative for Rh Disease Eradication (WIRhE); and CEO for Ferrous Wheel Consultants, LLC. J.C.Z. is a founder of Svalinn Therapeutics. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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