| First Author | Peek CB | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 1 | Pages | 86-92 |
| PubMed ID | 27773696 | Mgi Jnum | J:251929 |
| Mgi Id | MGI:6107102 | Doi | 10.1016/j.cmet.2016.09.010 |
| Citation | Peek CB, et al. (2017) Circadian Clock Interaction with HIF1alpha Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle. Cell Metab 25(1):86-92 |
| abstractText | Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1alpha (HIF1alpha) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1alpha targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1alpha in response to hypoxia. HIF1alpha bound directly to core clock gene promoters, and, when co-expressed with BMAL1, led to transactivation of PER2-LUC and HRE-LUC reporters. Further, genetic stabilization of HIF1alpha in Vhl(-/-) cells altered circadian transcription. Finally, induction of clock and HIF1alpha target genes in response to strenuous exercise varied according to the time of day in wild-type mice. Collectively, our results reveal bidirectional interactions between circadian and HIF pathways that influence metabolic adaptation to hypoxia. |
