Hypoxia-induced suppression of c-Myc by HIF-2α in human pulmonary endothelial cells attenuates TFAM expression.
Cell Signal
; 38: 230-237, 2017 10.
Article
in En
| MEDLINE
| ID: mdl-28709643
ABSTRACT
The adaptive response to hypoxia is mediated in large part by stabilization of the hypoxia-inducible factors, HIF-1α and HIF-2α. A hallmark of this response is the metabolic shift to decreased oxidative phosphorylation and increased glycolysis. We hypothesized that hypoxic responses would include a suppression of mitochondrial gene expression. We determined the effects of hypoxia on TFAM, a key mitochondrial transcription factor, in normal pulmonary artery endothelial cells. Hypoxia decreased gene expression of TFAM and that of its upstream regulator, the transcriptional co-activator PGC1ß. Although HIF-1α and HIF-2α pathways both contributed to hypoxia-mediated PGC1ß suppression, TFAM suppression was regulated solely by HIF-2α-dependent mechanisms. We found that HIF-2α suppresses TFAM by decreasing c-Myc expression. In addition, we show a role for c-Jun in this pathway, linking HIF-2α with attenuation of c-Jun activation. Taken together, these findings establish a new link between HIF-2α and MAPK-signaling that mediates the adaptive regulation of mitochondrial gene expression under low oxygen tension.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Proto-Oncogene Proteins c-myc
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Mitochondrial Proteins
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Endothelial Cells
/
DNA-Binding Proteins
/
Basic Helix-Loop-Helix Transcription Factors
Limits:
Humans
Language:
En
Journal:
Cell Signal
Year:
2017
Document type:
Article
Affiliation country:
United States