Evidence map›Paper›PMID 38513237›Full record

ArticleBlood2024

Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro.

Travis Nemkov, Alicia Key, Daniel Stephenson, Eric J Earley, Gregory R Keele, Ariel Hay, Pascal Amireault, Madeleine Casimir, Michaël Dussiot, Monika Dzieciatkowska and 14 more

Open access · greenAbstract read
In one paragraph

Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
16.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 44 citations in OpenAlex.

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  12. Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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  15. HypomorphicHemaSphere · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 11 institutions in 4 countries.

Travis NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.ORCID 0000-0001-8566-7119
Alicia KeyDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.ORCID 0000-0002-8787-8144
Daniel StephensonDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.
Eric J EarleyGenomics and Translational Research Center, RTI International, Research Triangle Park, NC.ORCID 0000-0001-6576-1319
Gregory R KeeleGenomics and Translational Research Center, RTI International, Research Triangle Park, NC.ORCID 0000-0002-1843-7900
Ariel HayDepartment of Pathology, University of Virginia, Charlottesville, VA.ORCID 0000-0002-9003-6415
Pascal AmireaultUniversité Paris Cité et Université des Antilles, INSERM, Biologie Intégrée du Globule Rouge, Paris, France.ORCID 0000-0002-5562-7586
Madeleine CasimirUniversité Paris Cité et Université des Antilles, INSERM, Biologie Intégrée du Globule Rouge, Paris, France.
Michaël DussiotUniversité Paris Cité et Université des Antilles, INSERM, Biologie Intégrée du Globule Rouge, Paris, France.
Monika DzieciatkowskaDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.ORCID 0000-0002-7296-4963
Xutao DengVitalant Research Institute, San Francisco, CA.
Mars StoneVitalant Research Institute, San Francisco, CA.
Steve KleinmanThe University of British Columbia, Victoria, BC, Canada.
Steven L SpitalnikDepartment of Pathology and Cell Biology, Columbia University, New York, NY.ORCID 0000-0002-8528-4561
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.ORCID 0000-0001-5054-838X
Philip J NorrisVitalant Research Institute, San Francisco, CA.ORCID 0000-0003-0526-2088
Gary A ChurchillThe Jackson Laboratory, Bar Harbor, ME.ORCID 0000-0001-9190-9284
Michael P BuschVitalant Research Institute, San Francisco, CA.
Nareg RoubinianDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-1063-6155
Grier P PageGenomics and Translational Research Center, RTI International, Research Triangle Park, NC.ORCID 0000-0003-2582-3786
James C ZimringDepartment of Pathology, University of Virginia, Charlottesville, VA.
Arduino ArduiniDepartment of Research and Development, CoreQuest Sagl, Lugano, Switzerland.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO.ORCID 0000-0002-2258-6490
University of Colorado Anschutz Medical Campus · USInserm · FRRTI International · USUniversity of California, San Francisco · USUniversity of Virginia · USColumbia University · USCoreQuest (Switzerland) · CHJackson Laboratory · USKaiser Permanente · USPacific Research Institute · USUniversity of British Columbia · CA

Funding

REDS-IV-P - CENTER FOR TRANSFUSION LABORATORY STUDIES (CTLS) - SARS-CoV-2/COVID-19 STUDIES75N92019D00033 · NHLBI · VITALANT · PI NORRIS, PHILIP J. · 2019 to 2024
$15.6M
New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
Defining the functions and translational potential of ferroptosisR35CA209896 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STOCKWELL, BRENT R. · 2016 to 2022
$6.5M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
Interactions between the ADORA2b/Sphk1axis and the AE1-Hb switch in red blood cell aging in vivo and in vitroR01HL149714 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2023
$2.6M
Effects of blood conservation and donor characteristics on transfused patient outcomes in a large community hospital networkR01HL126130 · NHLBI · VITALANT · PI ROUBINIAN, NAREG · 2016 to 2019
$1.9M
MIRAGES: Metabolic Investigation of Red blood cells as a function of Aging, Genetics, Environment, and StorageR21HL150032 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2021
$414k
Bayesian Modeling of Mass-Spec Proteomics Data to Advance Studies of the Genetic Regulation of ProteinsF32GM134599 · NIGMS · JACKSON LABORATORY · PI KEELE, GREGORY R · 2020 to 2021
$139k
NCI NIH HHS R35 CA209896NHLBI NIH HHS 75N92019D00033NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS R01 HL126130NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01 HL148151NHLBI NIH HHS R01 HL149714NHLBI NIH HHS R21 HL150032NIGMS NIH HHS F32 GM134599NIGMS NIH HHS R01 GM067945WHI NIH HHS HHSN268201100001C
6 · The paper itself

Abstract

abstractRecent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured l-carnitine and acyl-carnitines in 13 091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation study. Genome-wide association studies against 879 000 polymorphisms identified critical genetic factors contributing to interdonor heterogeneity in end-of-storage carnitine levels, including common nonsynonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, and SLC16A9); carnitine synthesis (FLVCR1 and MTDH) and metabolism (CPT1A, CPT2, CRAT, and ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying 2 alleles of the rs12210538 SLC22A16 single-nucleotide polymorphism exhibited the lowest l-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice, and Percoll density gradients of human RBCs, showed age-dependent depletions of l-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process after chemically induced membrane lipid damage. Supplementation of stored murine RBCs with l-carnitine boosted posttransfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.

Indexed as

CarnitineErythrocytesHemolysisAnimalsBlood PreservationErythrocyte AgingFemaleGenome-Wide Association StudyHumansMaleMicePolymorphism, Single NucleotideSolute Carrier Family 22 Member 5CarnitineSolute Carrier Family 22 Member 5

Identifiers

PMID38513237
PMCPMC11208298
OpenAlexW4393057611

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.