Dendritic cells (DC) are sentinels of the immune system deriving from circulating monocyte precursors recruited to sites of inflammation. In a previous report (Del Prete et al., 2008) we showed that, after differentiation, DC exhibited increased number of condensed mitochondria and dynamic changes in their energy metabolism. A study is presented here showing that the DC differentiation process is characterized by increased expression level and activity of mitochondrial respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy number. Moreover, DC are equipped with more efficient antioxidant protection systems, over expressed most likely to detoxify increased ROS production, as a consequence of the much higher mitochondrial activity. Kinetic analysis of the three main mitochondrial biogenesis-associated genes revealed that the peak in PPARγ coactivator-1alpha (PGC-1α) gene expression was suddenly reached few hours after the onset of the differentiation. While PGC-1α expression rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) expression gradually increased. These findings demonstrate that an active mitochondrial biogenesis occurs during DC differentiation and further suggest that an early input by the master regulator of mitochondrial biogenesis PGC-1α is needed to trigger the subsequent activation of the downstream transcription factors, NRF-1 and TFAM in this process.

An active mitochondrial biogenesis occurs during dendritic cell differentiation

SANTORO, Giuseppe;NICO, Beatrice;
2012-01-01

Abstract

Dendritic cells (DC) are sentinels of the immune system deriving from circulating monocyte precursors recruited to sites of inflammation. In a previous report (Del Prete et al., 2008) we showed that, after differentiation, DC exhibited increased number of condensed mitochondria and dynamic changes in their energy metabolism. A study is presented here showing that the DC differentiation process is characterized by increased expression level and activity of mitochondrial respiratory complexes, as well as by an increased mitochondrial DNA (mtDNA) copy number. Moreover, DC are equipped with more efficient antioxidant protection systems, over expressed most likely to detoxify increased ROS production, as a consequence of the much higher mitochondrial activity. Kinetic analysis of the three main mitochondrial biogenesis-associated genes revealed that the peak in PPARγ coactivator-1alpha (PGC-1α) gene expression was suddenly reached few hours after the onset of the differentiation. While PGC-1α expression rapidly declines, the mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) expression gradually increased. These findings demonstrate that an active mitochondrial biogenesis occurs during DC differentiation and further suggest that an early input by the master regulator of mitochondrial biogenesis PGC-1α is needed to trigger the subsequent activation of the downstream transcription factors, NRF-1 and TFAM in this process.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/130317
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