Abstract

Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing that UCP2 is mainly expressed in organs and cells associated with the immune system. Although the UCP2 gene is present in the brain, as demonstrated using quantitative RT-PCR, the protein was not detectable in neurons under physiological conditions. Instead, we could detect UCP2 in microglia, which act in the immune defense of the central nervous system. In lymphocytes, activation led to a ten-fold increase of UCP2 protein expression simultaneously to the increase in levels of other mitochondrial proteins, whereas lymphocyte re-stimulation resulted in the selective increase of UCP2. The highest detected level of UCP2 expression in stimulated T-cells (0.54 ng/(µg total cellular protein)) was approximately 200 times lower than the level of UCP1 in brown adipose tissue from room temperature acclimated mice. Both the UCP2 expression pattern and the time course of up-regulation in stimulated T-cells imply UCP2’s involvement in the immune response, probably by controlling the metabolism during cell proliferation.

Highlights

  • Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein, which belongs to the mitochondrial anion carrier superfamily [1,2] and is highly homologous to UCP3 (73%) and UCP1 (59%, [3])

  • In the present work we investigate UCP2 expression among different mouse tissues at the mRNA and protein levels focusing on cells of the nervous and immune systems

  • To test whether age differences may have contributed to the discrepancies in results, we compared UCP2 mRNA expression in different tissues of early postnatal (5 days old), young (30 days old) and adult (12 months old) C57BL/6 mice (Fig. 1). mRNA levels were determined by quantitative real-time PCR-analysis and presented as ratios of UCP2 to the housekeeping gene GAPDH

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Summary

Introduction

Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein, which belongs to the mitochondrial anion carrier superfamily [1,2] and is highly homologous to UCP3 (73%) and UCP1 (59%, [3]). The latter mediates non-shivering thermogenesis in brown adipose tissue (BAT) by dissipating a proton gradient across the inner mitochondrial membrane [4,5,6]. Experiments using artificial membranes support the idea that UCP2 transports protons in the presence of fatty acids and with high sensitivity to the membrane potential to UCP1 [7,8,9,10]. A possible explanation may be the difference in the expression levels of these proteins [11]

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