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bioRxiv · 10.1101/2020.07.01.181768

Mitochondrial uncoupling protein 2 (UCP2), but not UCP3, is sensitive to oxygen concentration in cells

Hilse, K. E.·Rupprecht, A.·Ford, K.·Andrukhova, O.·Erben, R.·Pohl, E. E.
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Abstract

One of the important hallmarks of cardiovascular disease is mitochondrial dysfunction, which results in abnormal energy metabolism and increased ROS production in cardiomyocytes. Members of the mitochondrial uncoupling protein family, UCP2 and UCP3, are thought to be beneficial by reducing ROS due to mild uncoupling. More recent hypotheses suggest the involvement of both proteins in cell metabolism by the transport of yet unknown substrates. The protein expression pattern under physiological and pathological conditions is an important clue for the evaluation of UCP2/UCP3 function, however, there is still no consensus about it. Previously, we demonstrated that only UCP3 is present in the adult murine heart under physiological conditions and correlated it with the predominant use of fatty acids for oxidation. In contrast, UCP2 was found only in very young (stem cell – like) cardiomyocytes, that rely mostly on glycolysis. Here, we employed three different models (ex vivo heart ischemia-reperfusion model, myocardial infarction model, and embryonic stem cell differentiation into cardiomyocytes under hypoxic conditions) to evaluate the abundance of both proteins under ischemia and hypoxia conditions. We found that (i) oxygen shortage or bursts did not influence UCP3 levels in the heart and ii) UCP2 was not present in healthy, ischemic, or re-perfused hearts. However, (iii) UCP2 was sensitive to the oxygen concentration in stem cells, in which UCP2 is normally expressed. These results further support the idea, that two highly homologous proteins – UCP2 and UCP3 – are abundant in different cells and tissues, and differently regulated under physiological and pathological conditions.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Hilse, K. E., Rupprecht, A., Ford, K., Andrukhova, O., Erben, R., Pohl, E. E.. 2020-07-02. Mitochondrial uncoupling protein 2 (UCP2), but not UCP3, is sensitive to oxygen concentration in cells. https://doi.org/10.1101/2020.07.01.181768

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