Skip to content
DraconiticResearch
Search Sources API
181,716 studies31 sourcesUpdated 13 min ago
Peer-reviewedCC BYNature

MCT1-dependent mitochondrial lactate import sustains cardiac metabolism

  • Ahmad A. Cluntun1,2,3
  • Joseph R. Visker4,5,6
  • Jesse N. Velasco‐Silva2,3
  • James Carrington2,7,8
  • Luis Cedeño-Rosario2,3
  • Giulia C. Napoli2,6
  • Ji Eon Kim2,9,6
  • Thirupura Sundari Shankar5,6
  • Marisa J. Lang10,3
  • Rana Hamouche5,3
  • Álvaro Jesús Narbona‐Pérez2,3
  • Jing Ling5,3
26 more authors
  • Ashish Ganeshlalji Toshniwal2,3
  • Hayden K. Low2,3,11
  • Corey Nathaniel Cunningham2,3,11
  • David Eberhardt5,3
  • Jing Li5,3
  • Claire E. Stanley2,3
  • Queren A. Alcantara2,3
  • Tarun Yadav2,12
  • Ryan L. Maves2,6
  • Wojciech Swiatek2,3
  • Nicholas Awuku Offei1,3
  • Bhavya Blaze1,13
  • Sumangala P. Shetty1,6
  • Dipayan Chaudhuri2,14,10,15,5,3
  • TingTing Hong16,5,3,17,18,6
  • Jeffrey D. Rothstein19,20
  • Deborah M. Muoio21
  • João A. Paulo22,23
  • Steven P. Gygi22,23
  • Eleni Tseliou15,5,24,13
  • Sutip Navankasattusas5,6
  • James Eric Cox2,25,3,11
  • Katsuhiko Funai26,2,10,3,7,8
  • Stavros Drakos27,28,29,18,6,30
  • Jared P. Rutter31,32,33,3,34
  • Gregory S. Ducker35,36,3
36 affiliations
  1. 1Department of Biochemistry and Molecular Biology, Rutgers University, Piscataway, NJ, USA
  2. 2Department of Biochemistry, University of Utah, Salt Lake City, UT, USA
  3. 3Department of Biochemistry, University of Utah, Salt Lake City, UT 842, USA
  4. 4Department of Cardiothoracic Surgery, and Section of Molecular Medicine, Department of Internal Medicine, Wake Forest University Health Science Center, Winston-Salem, NC, USA
  5. 5Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA
  6. 6Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 8411, USA
  7. 7Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA
  8. 8The Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 8112, USA
  9. 9Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea
  10. 10Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA
  11. 11Metabolomics, Proteomics and Mass Spectrometry Core Facility, University of Utah, Salt Lake City, UT 84112, USA
  12. 12High-throughput Genomics Core, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA
  13. 13University of Utah, Department of Pathology, Salt Lake City, UT 84112, USA
  14. 14Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA
  15. 15Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA
  16. 16Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
  17. 17Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA
  18. 18Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT 4112, USA
  19. 19Department of Neurology, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA
  20. 20Department of Neurology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
  21. 21Departments of Medicine and Pharmacology and Cancer Biology, and Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
  22. 22Department of Cell Biology, Harvard Medical School, Boston, MA, USA
  23. 23Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
  24. 24UTAH (Utah Transplant Affiliated Hospitals) Cardiac Transplant Program, University of Utah Healthcare and School of Medicine, Intermountain Medical Center, Salt Lake Veterans Affairs Health Care System, Salt Lake City, UT, USA
  25. 25Metabolomics, Proteomics and Mass Spectrometry Core Facility, University of Utah, Salt Lake City, UT, USA
  26. 26Center for Metabolic Health, University of Utah, Salt Lake City, UT, USA
  27. 27Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA. [email protected]
  28. 28Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA. [email protected]
  29. 29UTAH (Utah Transplant Affiliated Hospitals) Cardiac Transplant Program, University of Utah Healthcare and School of Medicine, Intermountain Medical Center, Salt Lake Veterans Affairs Health Care System, Salt Lake City, UT, USA. [email protected]
  30. 30U.T.A.H. (Utah Transplant Affiliated Hospitals) Cardiac Transplant Program: University of Utah Healthcare and School of Medicine, Intermountain Medical Center, Salt Lake VA (Veterans Affairs) Health Care System, Salt Lake City, UT, USA
  31. 31Center for Metabolic Health, University of Utah, Salt Lake City, UT, USA. [email protected]
  32. 32Department of Biochemistry, University of Utah, Salt Lake City, UT, USA. [email protected]
  33. 33Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. [email protected]
  34. 34Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
  35. 35Center for Metabolic Health, University of Utah, Salt Lake City, UT, USA. [email protected]
  36. 36Department of Biochemistry, University of Utah, Salt Lake City, UT, USA. [email protected]
Open at sourceDOICite

Abstract

Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC). Using 13 C stable isotope tracing, we demonstrated that lactate is oxidized in the myocardial tissue of mice even when the MPC is genetically deleted. This MPC-independent lactate import and mitochondrial oxidation is dependent upon the monocarboxylate transporter 1 (MCT1/ Slc16a1 ). Mitochondria isolated from the myocardium without MCT1 exhibit a specific defect in mitochondrial lactate, but not pyruvate, metabolism. The import and subsequent mitochondrial oxidation of lactate by mitochondrial lactate dehydrogenase (LDH) acts as an electron shuttle, generating sufficient NADH to support respiration even when the TCA cycle is disrupted. In response to diverse cardiac insults, animals with hearts lacking MCT1 undergo rapid progression to heart failure with reduced ejection fraction. Thus, the mitochondrial import and oxidation of lactate enables carbohydrate entry into the TCA cycle to sustain cardiac energetics and maintain myocardial structure and function under stress conditions.

Related

  1. Lactate dehydrogenase activity and carbohydrate metabolism under vanadium citrate exposure: Sex- and dose-dependent effects in rat tissues
    Ruslana Iskra, Halyna Klymets, Iryna Oliynyk
    PLOS OnePeer-reviewedCC BY 4.0Full textEnzymology & metabolismPhysiologyPLOS
  2. Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells
    Qinghui Shang, Xuepeng Bian, Shujie Lou
    Frontiers in cell and developmental biologyPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  3. Lactate dynamics at the Pseudomonas aeruginosa–host interface: bacterial metabolism, host defense, and emerging links to histone lactylation
    Yi Jian, Zhijie Wu, Yuqiang Liang +4
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMCCrossrefEurope PMC
  4. Lactate metabolism and protein lactylation in programmed cell death: From novel mechanism to therapeutic strategies in human diseases
    Yue Chen, Xiwen Wang, Xiuping Wang +6
    Clinical and Translational MedicinePeer-reviewedCC BYFull textMolecular biology & gene regulationDOAJ
  5. LncRNA CCDC152 coordinates a tumor-associated selenoprotein P cycle that sustains selenium-dependent redox homeostasis in glioblastoma.
    Stephanie Siu, Hiroki Taguchi, Xi Zheng +14
    Redox biologyPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMC

Cite

BibTeXRIS
BibTeX
@article{cluntun2026mct1dependent,
  title = {{MCT1-dependent mitochondrial lactate import sustains cardiac metabolism}},
  author = {Ahmad A. Cluntun and Joseph R. Visker and Jesse N. Velasco‐Silva and James Carrington and Luis Cedeño-Rosario and Giulia C. Napoli and Ji Eon Kim and Thirupura Sundari Shankar and Marisa J. Lang and Rana Hamouche and Álvaro Jesús Narbona‐Pérez and Jing Ling and Ashish Ganeshlalji Toshniwal and Hayden K. Low and Corey Nathaniel Cunningham and David Eberhardt and Jing Li and Claire E. Stanley and Queren A. Alcantara and Tarun Yadav and Ryan L. Maves and Wojciech Swiatek and Nicholas Awuku Offei and Bhavya Blaze and Sumangala P. Shetty and Dipayan Chaudhuri and TingTing Hong and Jeffrey D. Rothstein and Deborah M. Muoio and João A. Paulo and Steven P. Gygi and Eleni Tseliou and Sutip Navankasattusas and James Eric Cox and Katsuhiko Funai and Stavros Drakos and Jared P. Rutter and Gregory S. Ducker},
  journal = {Nature},
  year = {2026},
  month = oct,
  doi = {10.1038/s41586-026-11182-3},
  url = {https://doi.org/10.1038/s41586-026-11182-3},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - MCT1-dependent mitochondrial lactate import sustains cardiac metabolism
AU  - Ahmad A. Cluntun
AU  - Joseph R. Visker
AU  - Jesse N. Velasco‐Silva
AU  - James Carrington
AU  - Luis Cedeño-Rosario
AU  - Giulia C. Napoli
AU  - Ji Eon Kim
AU  - Thirupura Sundari Shankar
AU  - Marisa J. Lang
AU  - Rana Hamouche
AU  - Álvaro Jesús Narbona‐Pérez
AU  - Jing Ling
AU  - Ashish Ganeshlalji Toshniwal
AU  - Hayden K. Low
AU  - Corey Nathaniel Cunningham
AU  - David Eberhardt
AU  - Jing Li
AU  - Claire E. Stanley
AU  - Queren A. Alcantara
AU  - Tarun Yadav
AU  - Ryan L. Maves
AU  - Wojciech Swiatek
AU  - Nicholas Awuku Offei
AU  - Bhavya Blaze
AU  - Sumangala P. Shetty
AU  - Dipayan Chaudhuri
AU  - TingTing Hong
AU  - Jeffrey D. Rothstein
AU  - Deborah M. Muoio
AU  - João A. Paulo
AU  - Steven P. Gygi
AU  - Eleni Tseliou
AU  - Sutip Navankasattusas
AU  - James Eric Cox
AU  - Katsuhiko Funai
AU  - Stavros Drakos
AU  - Jared P. Rutter
AU  - Gregory S. Ducker
PY  - 2026
DA  - 2026/10/28
JO  - Nature
DO  - 10.1038/s41586-026-11182-3
UR  - https://doi.org/10.1038/s41586-026-11182-3
AB  - Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate is an important energy source for many organs, but first must be oxidized to pyruvate for entry into the tricarboxylic acid cycle (TCA cycle). This reaction is thought to occur in the cytosol, with pyruvate subsequently transported into mitochondria via the mitochondrial pyruvate carrier (MPC). Using 13 C stable isotope tracing, we demonstrated that lactate is oxidized in the myocardial tissue of mice even when the MPC is genetically deleted. This MPC-independent lactate import and mitochondrial oxidation is dependent upon the monocarboxylate transporter 1 (MCT1/ Slc16a1 ). Mitochondria isolated from the myocardium without MCT1 exhibit a specific defect in mitochondrial lactate, but not pyruvate, metabolism. The import and subsequent mitochondrial oxidation of lactate by mitochondrial lactate dehydrogenase (LDH) acts as an electron shuttle, generating sufficient NADH to support respiration even when the TCA cycle is disrupted. In response to diverse cardiac insults, animals with hearts lacking MCT1 undergo rapid progression to heart failure with reduced ejection fraction. Thus, the mitochondrial import and oxidation of lactate enables carbohydrate entry into the TCA cycle to sustain cardiac energetics and maintain myocardial structure and function under stress conditions.
SN  - 0028-0836
SN  - 1476-4687
ER  -