George 2015 Abstract MiPschool Greenville 2015
|Mitochondria do not directly oxidize lactate within the cerebral cortex or hippocampus.|
Event: MiPschool Greenville 2015
The nature and existence of mitochondrial lactate oxidation has been a contentious topic . 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 .
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.
Labels: MiParea: Respiration
Organism: Human, Mouse, Rat Tissue;cell: Skeletal muscle, Nervous system Preparation: Permeabilized tissue
Coupling state: OXPHOS Pathway: N
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
- Passarella S, Paventi G, Pizzuto R (2014) The mitochondrial L-lactate dehydrogenase affair. Frontiers Neurosc 8:407.
- 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.
- Jacobs RA, Meinild AK, Nordsborg NB, Lundby C (2013) Lactate oxidation in human skeletal muscle mitochondria. Am Jo Physiol-Endocrin Metabol 304:E686-94.
- 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.