| First Author | Jacobi D | Year | 2015 |
| Journal | Cell Metab | Volume | 22 |
| Issue | 4 | Pages | 709-20 |
| PubMed ID | 26365180 | Mgi Jnum | J:299576 |
| Mgi Id | MGI:6501243 | Doi | 10.1016/j.cmet.2015.08.006 |
| Citation | Jacobi D, et al. (2015) Hepatic Bmal1 Regulates Rhythmic Mitochondrial Dynamics and Promotes Metabolic Fitness. Cell Metab 22(4):709-20 |
| abstractText | Mitochondria undergo architectural/functional changes in response to metabolic inputs. How this process is regulated in physiological feeding/fasting states remains unclear. Here we show that mitochondrial dynamics (notably fission and mitophagy) and biogenesis are transcriptional targets of the circadian regulator Bmal1 in mouse liver and exhibit a metabolic rhythm in sync with diurnal bioenergetic demands. Bmal1 loss-of-function causes swollen mitochondria incapable of adapting to different nutrient conditions accompanied by diminished respiration and elevated oxidative stress. Consequently, liver-specific Bmal1 knockout (LBmal1KO) mice accumulate oxidative damage and develop hepatic insulin resistance. Restoration of hepatic Bmal1 activities in high-fat-fed mice improves metabolic outcomes, whereas expression of Fis1, a fission protein that promotes quality control, rescues morphological/metabolic defects of LBmal1KO mitochondria. Interestingly, Bmal1 homolog AHA-1 in C. elegans retains the ability to modulate oxidative metabolism and lifespan despite lacking circadian regulation. These results suggest clock genes are evolutionarily conserved energetics regulators. |
