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George 2015 Abstract MiPschool Greenville 2015

From Bioblast
Mitochondria do not directly oxidize lactate within the cerebral cortex or hippocampus.


George MAJ, Herbst EAF, Brebner K, Holloway GP, Kane DA (2015)

Event: MiPschool Greenville 2015

The nature and existence of mitochondrial lactate oxidation has been a contentious topic [1]. To determine whether lactate is oxidized in the matrix of brain mitochondria, respiratory oxygen flux (JO2) was measured in saponin-permeabilized mouse brain cortex samples, prepared as previously described [2].

While JO2 in the presence of ADP and malate was uninfluenced by addition of lactate, JO2 rose significantly following the addition of exogenous NAD+, suggesting the mechanism of lactate oxidation involves extra-matrix lactate dehydrogenase (LDH). Mitochondrial JO2 was comparable between glutamate, pyruvate and NAD+-dependent lactate oxidation. Mitochondrial JO2 supported by NAD+-dependent lactate oxidation was significantly decreased with the addition of ฮฑ-cyano-4-hydroxycinnamate, an inhibitor of mitochondrial pyruvate transport. In addition, mitochondrial JO2 supported by NAD+-dependent lactate oxidation was inhibited with addition of oxamate, a membrane impermeable LDH inhibitor. Similar observations were made within rat hippocampal (cornu ammonis 1; CA1) samples, suggesting the mechanism by which mitochondria oxidize lactate in rodent brain is not unique to cortex.

As with human and rat skeletal muscle [3,4], the current results support the interpretation that lactate oxidation occurs outside the mitochondrial matrix in mouse cortex and rat hippocampus.

โ€ข O2k-Network Lab: CA Guelph Holloway GP, CA Antigonish Kane DA

Labels: MiParea: Respiration 

Organism: Human, Mouse, Rat  Tissue;cell: Skeletal muscle, Nervous system  Preparation: Permeabilized tissue 

Coupling state: OXPHOS  Pathway:

Event: Poster 


1-Dept Human Kinetics, St Francis Xavier Univ, Nova Scotia; 2-Dept Human Health Nutritional Sc, Univ Guelph, Ontario; 3-Dept Psychology, St Francis Xavier Univ, Nova Scotia, Canada. - [email protected]

References and acknowledgements

  1. Passarella S, Paventi G, Pizzuto R (2014) The mitochondrial L-lactate dehydrogenase affair. Frontiers Neurosc 8:407.
  2. Herbst EA, Holloway GP (2015) Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain. The J Physiology 593:787-801.
  3. Jacobs RA, Meinild AK, Nordsborg NB, Lundby C (2013) Lactate oxidation in human skeletal muscle mitochondria. Am Jo Physiol-Endocrin Metabol 304:E686-94.
  4. Elustondo PA, White AE, Hughes M, Brebner K, Pavlov E, Kane DA (2013) Physical and functional association of lactate dehydrogenase (LDH) with skeletal muscle mitochondria. J Biolo Chem 288:25309-17.

Supported by: National Science and Engineering Research Council.

  • MAJG and EAFH contributed equally to this study.