Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes.
Document Type
Article
Publication Date
9-3-2024
Original Citation
Nemkov T,
Stephenson D,
Earley E,
Keele G,
Hay A,
Key A,
Haiman Z,
Erickson C,
Dzieciatkowska M,
Reisz J,
Moore A,
Stone M,
Deng X,
Kleinman S,
Spitalnik S,
Hod E,
Hudson K,
Hansen K,
Palsson B,
Churchill G,
Roubinian N,
Norris P,
Busch M,
Zimring J,
Page G,
D'Alessandro A.
Biological and genetic determinants of glycolysis: Phosphofructokinase isoforms boost energy status of stored red blood cells and transfusion outcomes. Cell Metab. 2024;36(9):1979–97.
Keywords
JMG, Humans, Glycolysis, Erythrocytes, Animals, Mice, Male, Female, Blood Preservation, Phosphofructokinases, Adult, Middle Aged, Adenosine Triphosphate, Hemolysis, Hexokinase, Energy Metabolism, Isoenzymes, Blood Transfusion, Aged
JAX Source
Cell Metab. 2024;36(9):1979–97.
ISSN
1932-7420
PMID
38964323
DOI
https://doi.org/10.1016/j.cmet.2024.06.007
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.