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Oxaloacetate Enhances Neuronal Cell Bioenergetic Fluxes and Infrastructure
Wilkins, Heather M. Koppel, Scott Carl, Steven M. Ramanujan, Suruchi Weidling, Ian Michaelis, Mary Lou Michaelis, Elias K. Swerdlow, Russell Howard
Wilkins, Heather M.
Koppel, Scott
Carl, Steven M.
Ramanujan, Suruchi
Weidling, Ian
Michaelis, Mary Lou
Michaelis, Elias K.
Swerdlow, Russell Howard
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Abstract
We tested how the addition of oxaloacetate (OAA) to SH-SY5Y cells affected bioenergetic fluxes and infrastructure, and compared the effects of OAA to malate, pyruvate, and glucose deprivation. OAA displayed pro-glycolysis and pro-respiration effects. OAA pro-glycolysis effects were not a consequence of decarboxylation to pyruvate because unlike OAA, pyruvate lowered the glycolysis flux. Malate did not alter glycolysis flux and reduced mitochondrial respiration. Glucose deprivation essentially eliminated glycolysis and increased mitochondrial respiration. OAA increased, while malate decreased, the cell NAD+/NADH ratio. Cytosolic malate dehydrogenase 1 (MDH1) protein increased with OAA treatment, but not with malate or glucose deprivation. Glucose deprivation increased protein levels of ATP citrate lyase, an enzyme which produces cytosolic OAA, while OAA altered neither ATP citrate lyase mRNA nor protein levels. OAA, but not glucose deprivation, increased COX2, PGC1α, PGC1β, and PRC protein levels. OAA increased total and phosphorylated SIRT1 protein. We conclude that adding OAA to SH-SY5Y cells can support or enhance both glycolysis and respiration fluxes. These effects appear to depend, at least partly, on OAA causing a shift in the cell redox balance to a more oxidized state, that it is not a glycolysis pathway intermediate, and possibly its ability to act in an anaplerotic fashion.
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"This is the peer reviewed version of the following article: Wilkins, Heather M. et al. “Oxaloacetate Enhances Neuronal Cell Bioenergetic Fluxes and Infrastructure.” Journal of neurochemistry 137.1 (2016): 76–87., which has been published in final form at 10.1111/jnc.13545. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
Date
2016-03-11
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Wiley
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Keywords
Bioenergetics, Glycolysis, Mitochondria, Oxaloacetate, Respiration
Citation
Wilkins, Heather M. et al. “Oxaloacetate Enhances Neuronal Cell Bioenergetic Fluxes and Infrastructure.” Journal of neurochemistry 137.1 (2016): 76–87.