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Drosophila melanogaster activating transcription factor 4 regulates glycolysis during endoplasmic reticulum stress.

Lee JE, Oney M, Frizzell K, Phadnis N, Hollien J - G3 (Bethesda) (2015)

Bottom Line: The unfolded protein response transcription factor Atf4 was necessary for the up-regulation of glycolytic enzymes and Lactate dehydrogenase (Ldh).Finally, flies up-regulated Ldh and produced more lactate when subjected to ER stress.Together, these results suggest that Atf4 mediates a shift from a metabolism based on oxidative phosphorylation to one more heavily reliant on glycolysis, reminiscent of aerobic glycolysis or the Warburg effect observed in cancer and other proliferative cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112.

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Metabolic gene expression is regulated by Tm in S2 cells. We treated S2 cells with Tm (5 μg/mL) and measured relative RNA levels by quantitative polymerase chain reaction. We normalized all RNA measurements to the RNA levels of Ribosomal protein L19 (RpL19). Data are presented as means ± SEs of three technical replicates, and are representative of two independent experiments. Pfk, phosphofructokinase; TCA, tricarboxylic acid; Tm, tunicamycin; Tpi, triosephosphate isomerase.
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fig2: Metabolic gene expression is regulated by Tm in S2 cells. We treated S2 cells with Tm (5 μg/mL) and measured relative RNA levels by quantitative polymerase chain reaction. We normalized all RNA measurements to the RNA levels of Ribosomal protein L19 (RpL19). Data are presented as means ± SEs of three technical replicates, and are representative of two independent experiments. Pfk, phosphofructokinase; TCA, tricarboxylic acid; Tm, tunicamycin; Tpi, triosephosphate isomerase.

Mentions: To confirm these findings and to determine whether the expression changes were specific to DTT or a general response to ER stress, we treated S2 cells with another ER stress reagent, Tm (5 μg/mL), which inhibits N-linked glycosylation. We then monitored RNA levels of several genes over time, by qPCR (Figure 2). Consistent with the microarray results, expression of glycolytic genes and Ldh was increased and expression of genes encoding TCA cycle enzymes and respiratory chain complexes was decreased in response to Tm.


Drosophila melanogaster activating transcription factor 4 regulates glycolysis during endoplasmic reticulum stress.

Lee JE, Oney M, Frizzell K, Phadnis N, Hollien J - G3 (Bethesda) (2015)

Metabolic gene expression is regulated by Tm in S2 cells. We treated S2 cells with Tm (5 μg/mL) and measured relative RNA levels by quantitative polymerase chain reaction. We normalized all RNA measurements to the RNA levels of Ribosomal protein L19 (RpL19). Data are presented as means ± SEs of three technical replicates, and are representative of two independent experiments. Pfk, phosphofructokinase; TCA, tricarboxylic acid; Tm, tunicamycin; Tpi, triosephosphate isomerase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390581&req=5

fig2: Metabolic gene expression is regulated by Tm in S2 cells. We treated S2 cells with Tm (5 μg/mL) and measured relative RNA levels by quantitative polymerase chain reaction. We normalized all RNA measurements to the RNA levels of Ribosomal protein L19 (RpL19). Data are presented as means ± SEs of three technical replicates, and are representative of two independent experiments. Pfk, phosphofructokinase; TCA, tricarboxylic acid; Tm, tunicamycin; Tpi, triosephosphate isomerase.
Mentions: To confirm these findings and to determine whether the expression changes were specific to DTT or a general response to ER stress, we treated S2 cells with another ER stress reagent, Tm (5 μg/mL), which inhibits N-linked glycosylation. We then monitored RNA levels of several genes over time, by qPCR (Figure 2). Consistent with the microarray results, expression of glycolytic genes and Ldh was increased and expression of genes encoding TCA cycle enzymes and respiratory chain complexes was decreased in response to Tm.

Bottom Line: The unfolded protein response transcription factor Atf4 was necessary for the up-regulation of glycolytic enzymes and Lactate dehydrogenase (Ldh).Finally, flies up-regulated Ldh and produced more lactate when subjected to ER stress.Together, these results suggest that Atf4 mediates a shift from a metabolism based on oxidative phosphorylation to one more heavily reliant on glycolysis, reminiscent of aerobic glycolysis or the Warburg effect observed in cancer and other proliferative cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112.

Show MeSH
Related in: MedlinePlus