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.
| Original language | English |
|---|---|
| Pages (from-to) | 1962-1969 |
| Number of pages | 8 |
| Journal | International Journal of Biochemistry and Cell Biology |
| Volume | 44 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2012 |
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Keywords
- Anti-oxidant enzymes
- Dendritic cell differentiation
- Mitochondrial biogenesis
- Mitochondrial respiratory complexes
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
Cite this
An active mitochondrial biogenesis occurs during dendritic cell differentiation. / Zaccagnino, Patrizia; Saltarella, Maddalena; Maiorano, Stefania; Gaballo, Antonio; Santoro, Giuseppe; Nico, Beatrice; Lorusso, Michele; Del Prete, Annalisa.
In: International Journal of Biochemistry and Cell Biology, Vol. 44, No. 11, 11.2012, p. 1962-1969.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An active mitochondrial biogenesis occurs during dendritic cell differentiation
AU - Zaccagnino, Patrizia
AU - Saltarella, Maddalena
AU - Maiorano, Stefania
AU - Gaballo, Antonio
AU - Santoro, Giuseppe
AU - Nico, Beatrice
AU - Lorusso, Michele
AU - Del Prete, Annalisa
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - Anti-oxidant enzymes
KW - Dendritic cell differentiation
KW - Mitochondrial biogenesis
KW - Mitochondrial respiratory complexes
UR - http://www.scopus.com/inward/record.url?scp=84864805602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864805602&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2012.07.024
DO - 10.1016/j.biocel.2012.07.024
M3 - Article
C2 - 22871569
AN - SCOPUS:84864805602
VL - 44
SP - 1962
EP - 1969
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
SN - 1357-2725
IS - 11
ER -