Abstract
Energy metabolism in the adult brain consumes large quantities of glucose, but little is known to date regarding how glucose metabolism changes during neuronal differentiation, a process that is highly demanding energetically. We studied changes in glucose metabolism during neuronal differentiation of P19 mouse embryonal carcinoma cells, E14Tg2A embryonic stem cells as well as during brain development of BLC57 mice. In all these models, we find that neurogenesis is accompanied by a shift from oxidative to fermentative glucose metabolism. This shift is accompanied by both a decrease in mitochondrial enzymatic activities and mitochondrial uncoupling. In keeping with this finding, we also observe that differentiation does not require oxidative metabolism, as indicated by experiments demonstrating that the process is preserved in cells treated with the ATP synthase inhibitor oligomycin. Overall, we provide evidence that neuronal differentiation involves a shift from oxidative to fermentative metabolism, and that oxidative phosphorylation is not essential for this process.
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Supplementary Figure 1
Viability of undifferentiated (UND) P19 cells and cells following completion of neuronal differentiation (DIF). Cell viability was detected by staining for 1 min with 0.004% Trypan Blue as stated in Experimental Procedures. (JPEG 961 kb)
Supplementary Figure 2
O2 consumption of P19 cells differentiated in the absence of cytosine-arabinoside. Cells were incubated with Krebs buffer and O2 consumption was estimated as described in Experimental Procedures. Cells were differentiated in the absence of 5 μg/ml cytosine arabinoside which was used to eliminate proliferating glial cells. (JPEG 972 kb)
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Fornazari, M., Nascimento, I.C., Nery, A.A. et al. Neuronal differentiation involves a shift from glucose oxidation to fermentation. J Bioenerg Biomembr 43, 531–539 (2011). https://doi.org/10.1007/s10863-011-9374-3
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DOI: https://doi.org/10.1007/s10863-011-9374-3