Lactate is oxidized outside of the mitochondrial matrix in rodent brain

Eric A. F. Herbst, Mitchell A. J. George, Karen Brebner, Graham P. Holloway, Daniel A. Kane*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
32 Downloads (Pure)


The nature and existence of mitochondrial lactate oxidation is debated in the literature. Obscuring the issue are disparate findings in isolated mitochondria, as well as relatively low rates of lactate oxidation observed in permeabilized muscle fibres. However, respiration with lactate has yet to be directly assessed in brain tissue with the mitochondrial reticulum intact. To determine if lactate is oxidized in the matrix of brain mitochondria, oxygen consumption was measured in saponin-permeabilized mouse brain cortex samples, and rat prefrontal cortex and hippocampus (dorsal) subregions. While respiration in the presence of ADP and malate increased with the addition of lactate, respiration was maximized following the addition of exogenous NAD+, suggesting maximal lactate metabolism involves extra-matrix lactate dehydrogenase. This was further supported when NAD+-dependent lactate oxidation was significantly decreased with the addition of either low-concentration α-cyano-4-hydroxycinnamate or UK-5099, inhibitors of mitochondrial pyruvate transport. Mitochondrial respiration was comparable between glutamate, pyruvate, and NAD+-dependent lactate oxidation. Results from the current study demonstrate that permeabilized brain is a feasible model for assessing lactate oxidation, and support the interpretation that lactate oxidation occurs outside the mitochondrial matrix in rodent brain.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalApplied Physiology, Nutrition and Metabolism
Issue number5
Publication statusPublished - May 2018
Externally publishedYes

Bibliographical note

Copyright the Author(s). Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Brain
  • Lactate
  • Lactate dehydrogenase
  • Mitochondria
  • Respiration


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