1. Role of UCP2 in the energy metabolism of the cancer cell line A549
- Author
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Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, European Commission, Segalés, Jessica [0000-0003-3565-0014], Sánchez-Martín, Carlos [0000-0001-5223-4798], Pujol, Aleida [0000-0002-7263-9394], Martín-Ruiz, Marta [0000-0003-0711-8979], Lobato-Alonso, Daniel [0009-0003-8118-4306], Oliver, Eduardo [0000-0001-9340-882X], Rial, Eduardo [0000-0001-8634-8902], Segalés, Jessica, Sánchez-Martín, Carlos, Pujol, Aleida, Martín-Ruiz, Marta, De los Santos, Patricia, Lobato-Alonso, Daniel, Oliver, Eduardo, Rial, Eduardo, Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, European Commission, Segalés, Jessica [0000-0003-3565-0014], Sánchez-Martín, Carlos [0000-0001-5223-4798], Pujol, Aleida [0000-0002-7263-9394], Martín-Ruiz, Marta [0000-0003-0711-8979], Lobato-Alonso, Daniel [0009-0003-8118-4306], Oliver, Eduardo [0000-0001-9340-882X], Rial, Eduardo [0000-0001-8634-8902], Segalés, Jessica, Sánchez-Martín, Carlos, Pujol, Aleida, Martín-Ruiz, Marta, De los Santos, Patricia, Lobato-Alonso, Daniel, Oliver, Eduardo, and Rial, Eduardo
- Abstract
The uncoupling protein UCP2 is a mitochondrial carrier for which transport activity remains controversial. The physiological contexts in which UCP2 is expressed have led to the assumption that, like UCP1, it uncouples oxidative phosphorylation and thereby reduces the generation of reactive oxygen species. Other reports have involved UCP2 in the Warburg effect, and results showing that UCP2 catalyzes the export of matrix C4 metabolites to facilitate glutamine utilization suggest that the carrier could be involved in the metabolic adaptations required for cell proliferation. We have examined the role of UCP2 in the energy metabolism of the lung adenocarcinoma cell line A549 and show that UCP2 silencing decreased the basal rate of respiration, although this inhibition was not compensated by an increase in glycolysis. Silencing did not lead to either changes in proton leakage, as determined by the rate of respiration in the absence of ATP synthesis, or changes in the rate of formation of reactive oxygen species. The decrease in energy metabolism did not alter the cellular energy charge. The decreased cell proliferation observed in UCP2-silenced cells would explain the reduced cellular ATP demand. We conclude that UCP2 does not operate as an uncoupling protein, whereas our results are consistent with its activity as a C4-metabolite carrier involved in the metabolic adaptations of proliferating cells.
- Published
- 2023