PMID:22898868

Citation	Amoroso, F, Falzoni, S, Adinolfi, E, Ferrari, D and Di Virgilio, F (2012) The P2X7 receptor is a key modulator of aerobic glycolysis. Cell Death Dis 3:e370
Abstract	Ability to adapt to conditions of limited nutrient supply requires a reorganization of the metabolic pathways to balance energy generation and production of biosynthetic intermediates. Several fast-growing cells overexpress the P2X7 receptor (P2X7R) for extracellular ATP. A feature of this receptor is to allow growth in the absence of serum. We show here that transfection of P2X7R allows proliferation of P2X7R-transfected HEK293 (HEK293-P2X7) cells not only in the absence of serum but also in low (4 mM) glucose, and increases lactate output compared with mock-transfected HEK293 (HEK293-mock) cells. In HEK293-P2X7, lactate output is further stimulated upon addition of exogenous ATP or the mitochondrial uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP). In the human neuroblastoma cell line ACN, lactate output is also dependent on P2X7R function. P2X7R-expressing cells upregulate (a) the glucose transporter Glut1, (b) the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), (c) phosphofructokinase (PFK), (d) pyruvate kinase M2 (PKM2) and (e) pyruvate dehydrogenase kinase 1 (PDHK1); furthermore, P2X7R expression (a) inhibits pyruvate dehydrogenase (PDH) activity, (b) increases phosphorylated Akt/PKB and hypoxia-inducible factor 1α (HIF-1α) expression and (c) enhances intracellular glycogen stores. In HEK293-P2X7 cells, glucose deprivation increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level. These data show that the P2X7R has an intrinsic ability to reprogram cell metabolism to meet the needs imposed by adverse environmental conditions.
Links	PubMed PMC3434661 Online version:10.1038/cddis.2012.105
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:P2RX7		GO:0010628: positive regulation of gene expression	ECO:0000315:		P		Figure 4-P2X7R expression causes overexpression of the key glycolytic enzymes G3PDH and PFK.	complete CACAO 5234
HUMAN:P2RX7		GO:0045821: positive regulation of glycolysis	ECO:0000315:		P		From figure 1 it shows that P2X7R expression stimulates cell metabolism	complete CACAO 5347
HUMAN:P2RX7	involved_in	GO:0045821: positive regulation of glycolytic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:P2RX7	involved_in	GO:0010628: positive regulation of gene expression	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
PIG:Q5DKW6		GO:0006091: generation of precursor metabolites and energy	ECO:0000315:		P		Figure 1 shows that P2X7R is involved in energy metabolism.	complete CACAO 5424

References

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