Brief communication

Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex

Eric A.F. Herbst, Graham P. Holloway

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.

Corresponding author: Graham P. Holloway (email: ghollowa@uoguelph.ca).

Copyright remains with the author(s) or their institution(s). Permission for reuse (free in most cases) can be obtained from RightsLink.

Published on the web 17 May 2016.

Received January 20, 2016. Accepted March 14, 2016.

Applied Physiology, Nutrition, and Metabolism, 2016, 41(7): 799-801, https://doi.org/10.1139/apnm-2016-0033

Abstract

The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate–aspartate shuttle.

Keywords: glutamate metabolism, exercise, brain mitochondria, cerebral cortex

References

Cheeseman AJ, Clark JB. 1988. Influence of the malate-aspartate shuttle on oxidative metabolism in synaptosomes. J. Neurochem. 50: 1559-1565 Crossref, Medline, Google Scholar.
Contreras L, Satrústegui J. 2009. Calcium signaling in brain mitochondria: interplay of malate aspartate NADH shuttle and calcium uniporter/mitochondrial dehydrogenase pathways. J. Biol. Chem. 284: 7091-7099 Crossref, Medline, Google Scholar.
Danbolt NC. 2001. Glutamate uptake. Prog. Neurobiol. 65: 1-105 Crossref, Medline, Google Scholar.
Elustondo PA, White AE, Hughes ME, Brebner K, Pavlov E, Kane DA. 2013. Physical and functional association of lactate dehydrogenase (LDH) with skeletal muscle mitochondria. J. Biol. Chem. 288: 25309-25317 Crossref, Medline, Google Scholar.
Estrada-Sánchez AM, Montiel T, Segovia J, Massieu L. 2009. Glutamate toxicity in the striatum of the R6/2 Huntington’s disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol. Dis. 34: 78-86 Crossref, Medline, Google Scholar.
Fiermonte G, Palmieri L, Todisco S, Agrimi G, Palmieri F, Walker JE. 2002. Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. J. Biol. Chem. 277: 19289-19294 Medline, Google Scholar.
Gellerich FN, Gizatullina Z, Trumbekaite S, Korzeniewski B, Gaynutdinov T, Seppet E, et al. 2012. Cytosolic Ca²⁺ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle. Biochem. J. 443: 747-755 Crossref, Medline, Google Scholar.
Hassel B, Tessler S, Faull RL, Emson PC. 2008. Glutamate uptake is reduced in prefrontal cortex in Huntington’s disease. Neurochem. Res. 33: 232-237 Crossref, Medline, Google Scholar.
Herbst EA, Holloway GP. 2015a. Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain. J. Physiol. 593: 787-801 Crossref, Medline, Google Scholar.
Herbst EAF, Holloway GP. 2015b. Exercise training normalizes mitochondrial respiratory capacity within the striatum of the R6/1 model of Huntington’s disease. Neuroscience 303: 513-523 Crossref, Medline, Google Scholar.
Herbst EAF, Roussakis C, Matravadia S, Holloway GP. 2015. Chronic treadmill running does not enhance mitochondrial oxidative capacity in the cortex or striatum. Metabolism 64: 1419-1425 Crossref, Medline, Google Scholar.
Kane DA. 2014. Lactate oxidation at the mitochondria: a lactate-malate-aspartate shuttle at work. Front. Neurosci. 8: 366 Crossref, Medline, Google Scholar.
McKenna MC. 2007. The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J. Neurosci. Res. 85: 3347-3358 Crossref, Medline, Google Scholar.
McKenna MC, Sonnewald U, Huang X, Stevenson J, Zielke HR. 1996. Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. J. Neurochem. 66: 386-393 Crossref, Medline, ISI, Google Scholar.
McKenna MC, Stevenson JH, Huang X, Hopkins IB. 2000. Differential distribution of the enzymes glutamate dehydrogenase and aspartate aminotransferase in cortical synaptic mitochondria contributes to metabolic compartmentation in cortical synaptic terminals. Neurochem. Int. 37: 229-241 Crossref, Medline, Google Scholar.
Palmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, et al. 2001. Citrin and aralar1 are Ca²⁺-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 20: 5060-5069 Crossref, Medline, Google Scholar.
Pang TY, Stam NC, Nithianantharajah J, Howard ML, Hannan AJ. 2006. Differential effects of voluntary physical exercise on behavioral and brain-derived neurotrophic factor expression deficits in Huntington’s disease transgenic mice. Neuroscience 141(2): 569-584 Crossref, Medline, Google Scholar.
Pardo B, Contreras L, Serrano A, Ramos M, Kobayashi K, Iijima M, et al. 2006. Essential role of aralar in the transduction of small Ca²⁺ signals to neuronal mitochondria. J. Biol. Chem. 281: 1039-1047 Crossref, Medline, Google Scholar.
Pellerin L, Magistretti PJ. 1994. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. 91: 10625-10629 Crossref, Medline, Google Scholar.
Ramos M, del Arco A, Pardo B, Martínez-Serrano A, Martínez-Morales JR, Kobayashi K, et al. 2003. Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Brain Res. Dev. Brain Res. 143: 33-46 Crossref, Medline, Google Scholar.
Rothman DL, Behar KL, Hyder F, Shulman RG. 2003. In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu. Rev. Physiol. 65: 401-427 Crossref, Medline, Google Scholar.
Van Dellen A, Blakemore C, Deacon R, York D, Hannan AJ. 2000. Delaying the onset of Huntington’s in mice. Nature 404(6779): 721-722 Crossref, Medline, Google Scholar.