| First Author | Vaughan ME | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 7 | Pages | 101338 |
| PubMed ID | 32683313 | Mgi Jnum | J:338653 |
| Mgi Id | MGI:6717750 | Doi | 10.1016/j.isci.2020.101338 |
| Citation | Vaughan ME, et al. (2020) Cryptochromes Suppress HIF1alpha in Muscles. iScience 23(7):101338 |
| abstractText | Muscles preferentially utilize glycolytic or oxidative metabolism depending on the intensity of physical activity. Transcripts required for carbohydrate and lipid metabolism undergo circadian oscillations of expression in muscles, and both exercise capacity and the metabolic response to exercise are influenced by time of day. The circadian repressors CRY1 and CRY2 repress peroxisome proliferator-activated receptor delta (PPARdelta), a major driver of oxidative metabolism and exercise endurance. CRY-deficient mice exhibit enhanced PPARdelta activation and greater maximum speed when running on a treadmill but no increase in exercise endurance. Here we demonstrate that CRYs limit hypoxia-responsive transcription via repression of HIF1alpha-BMAL1 heterodimers. Furthermore, CRY2 appeared to be more effective than CRY1 in the reduction of HIF1alpha protein steady-state levels in primary myotubes and quadriceps in vivo. Finally, CRY-deficient myotubes exhibit metabolic alterations consistent with cryptochrome-dependent suppression of HIF1alpha, which likely contributes to circadian modulation of muscle metabolism. |
