ArticleScience (New York, N.Y.)2024
Metabolic inflexibility promotes mitochondrial health during liver regeneration.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42citing papers in PubMed
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Who cites it
42 citing papers in PubMed.
- Dietary omega-6 lipids promote postinjury aberrant bone formation in obesity.The Journal of clinical investigation · 2026Article
- Hepatocyte-Specific RORα Deficiency Accelerates Liver Regeneration by Unleashing ME1-Driven Glycolysis.Genes · 2026Article
- From Collapse to Active Self-Repair: Integrative Multi-Omics and Machine Learning Analysis Map the Hepatic Metabolic Adaption in Response to Simulated Spaceflight Stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hyperpolarized MRI Detects Increased [1-NMR in biomedicine · 2026Article
- Oxidative stress drives liver failure during in vivo partial reprogramming.Molecules and cells · 2026Article
- Mitochondrial NADH-redox inflexibility constrains genomic and epigenetic stability in pluripotent stem cells.The EMBO journal · 2026Article
- Age-driven marbling in Haimen goat meat: multi-omics dissection of lipid/amino signatures and IMF regulatory networks.Food chemistry: X · 2026Article
- A Viscous DES-AAV-Foxo1 Delivery System With High Transfection Efficiency for the Treatment of Corneal Endothelial Dysfunction by Restoring Mitochondria-ER Contacts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gut Mycobiota-Associated Tryptophan Catabolites Protect Against Metabolic Dysfunction-Associated Steatotic Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026Review
- Glutathione peroxidase 3 preserves hepatocyte mitochondrial quality control to enhance macrophage pro-regenerative phenotype during liver regeneration.Clinical and translational medicine · 2026Article
- A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- YAP Induces a Prorenewal Metabolic State in Cardiomyocytes.Circulation · 2026Article
- Dual control of liver regeneration by Nr1d1 homeostasis and Klf2 checkpoint.Cell death discovery · 2026Article
- SLC13A2-transported citrate remodels transcriptional regulation through protein acetylation to suppress tumor growth.Science advances · 2026Article
- Stem cell functionbioRxiv : the preprint server for biology · 2026Article
- Type 2 Diabetes Mellitus as a Multisystem Disease: From Insulin Resistance to Organ Crosstalk-A Narrative Review.Biomedicines · 2026Review
- UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial Metabolomics Reveals the Mechanism of SCCP Induced Energy Metabolism Inhibition.Environmental science & technology · 2026Article
- Transient steatosis reprograms MDMs for liver repair.Nature metabolism · 2026Article
Corrections and comments
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Authors and funding
26 authors.
Xun WangChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-5172-0305
Cameron J MenezesChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-5759-8099
Yuemeng JiaChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-8019-1534
Yi XiaoChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-3817-3471
Siva Sai Krishna VenigallaChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-6795-2530
Feng CaiChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-5192-9520
Meng-Hsiung HsiehChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-9791-1318
Wen GuChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-3003-8945
Liming DuChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-0527-3556
Jessica SudderthChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Dohun KimChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-6060-0601
Spencer D SheltonChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0003-1236-5317
Claire B LlamasChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-4459-773X
Yu-Hsuan LinChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-7910-570X
Min ZhuChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Salma MerchantChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Divya BezwadaChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-5434-2976
Sherwin KelekarChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-7311-2965
Lauren G ZachariasChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Thomas P MathewsChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-9355-8243
Gerta HoxhajChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-6179-3583
R Max WynnDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-1879-2136
Uttam K TambarDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0001-5659-5355
Ralph J DeBerardinisChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-2705-7432
Hao ZhuChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-8417-9698
Prashant MishraChildren's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0003-2223-1742
Funding
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V. · 1996 to 2024
$57.4MUT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7MMetabolic Regulators of Tumor Growth and ProgressionR35CA220449 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI RALPH J DEBERARDINIS · 2017 to 2026
$9.4MUT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeffrey M Zigman · 2022 to 2026
$7.4MDIVISION OF CELL &MOLECULAR BIOLOGY TRAINING PROGRAMT32GM008203 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI COBB, MELANIE H. · 1987 to 2018
$7.0MStructure and Function of Mitochondrial Protein KinasesR01DK062306 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI CHUANG, DAVID T · 2003 to 2018
$5.4MDetermining how chronic ETOH influences the regenerative activities of hepatocyte subpopulationsR01AA028791 · NIAAA · UT SOUTHWESTERN MEDICAL CENTER · PI ZHU, HAO · 2021 to 2025
$2.7MEngineering faithful animal models of mitochondrial diseaseDP2ES030449 · NIEHS · UT SOUTHWESTERN MEDICAL CENTER · PI MISHRA, PRASHANT · 2018 to 2018
$2.4MDeciphering the role of amino acid transporters in mitochondrial myopathyR01AR073217 · NIAMS · UT SOUTHWESTERN MEDICAL CENTER · PI MISHRA, PRASHANT · 2018 to 2022
$1.8MInvestigating imitation SWI chromatin remodeling complexes in mammalian tissue regenerationR01DK125396 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI ZHU, HAO · 2020 to 2023
$1.5MUT Southwestern Center for Translational Medicine (UL18Kl2/TL1)TL1TR001104 · NCATS · UT SOUTHWESTERN MEDICAL CENTER · PI TOTO, ROBERT DANIEL · 2013 to 2017
$418kDefining mechanisms of metabolic-epigenetic crosstalk that drive glioma initiationK99CA277576 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI XIAO, YI · 2023 to 2024
$248kNCATS NIH HHS TL1 TR001104NCI NIH HHS F30 CA254150NCI NIH HHS F31 CA239330NCI NIH HHS K99 CA277576NCI NIH HHS P30 CA142543NCI NIH HHS P50 CA070907NCI NIH HHS R35 CA220449NIAAA NIH HHS R01 AA028791NIAMS NIH HHS R01 AR073217NIDDK NIH HHS F30 DK137407NIDDK NIH HHS P30 DK127984NIDDK NIH HHS R01 DK062306NIDDK NIH HHS R01 DK125396NIEHS NIH HHS DP2 ES030449NIGMS NIH HHS T32 GM008203NIH HHS S10 OD032267
Abstract
Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)-dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial β-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.
Indexed as
Acetyl Coenzyme AHepatocytesLiver RegenerationMitochondria, LiverPyruvic AcidAnimalsCell ProliferationElectron TransportFatty AcidsLiverMaleMiceMice, Inbred C57BLMitochondriaOxidation-ReductionAcetyl Coenzyme AFatty AcidsPyruvic Acid
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Read underepoch 390
Registered trials
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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.