George 2015 Abstract MiPschool Greenville 2015

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

Link:

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 α-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.

• 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: N 

Event: Poster 

Affiliations

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.