The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Hepatic Bmal1 Regulates Rhythmic Mitochondrial Dynamics and Promotes Metabolic Fitness
Open accessAbstract
SUMMARY 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 homologue 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.
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Cites
Mitochondrial Fission, Fusion, and Stress
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Reactive oxygen species have a causal role in multiple forms of insulin resistance
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“Increased oxidative stress is linked to insulin resistance (Houstis et al., 2006).”
BackgroundCircadian integration of metabolism and energetics
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Transcriptional architecture and chromatin landscape of the core circadian clock in mammals
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Self-citationMitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
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Physiological significance of a peripheral tissue circadian clock
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Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
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The PINK1/Parkin pathway regulates mitochondrial morphology
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Cited by
Circadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733
Crosstalk between metabolism and circadian clocks
Reinke, H., & Asher, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0096-9 · Cited by 598
Quality control of the mitochondrion
Ng, M. Y. W., Wai, T., & Simonsen, A. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.009 · Cited by 445
Circadian System and Glucose Metabolism: Implications for Physiology and Disease
Qian, J., & Scheer, F. A. J. L. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.03.005 · Cited by 365
Circadian Clock Control of Liver Metabolic Functions
Reinke, H., & Asher, G. (2016) · Gastroenterology · doi:10.1053/j.gastro.2015.11.043 · Cited by 321
Metadata
- Authors
- Jacobi, D., Liu, S., Burkewitz, K., Kory, N., Knudsen, N. H., Alexander, R. K., Unluturk, U., Li, X., Kong, X., Hyde, A. L., Gangl, M. R., Mair, W. B., & Lee, C.-H.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 22
- Issue
- 4
- Pages
- 709-720
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1911639929
- Cited by
- 409
- References
- 15
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Jacobi, D., Liu, S., Burkewitz, K., Kory, N., Knudsen, N. H., Alexander, R. K., Unluturk, U., Li, X., Kong, X., Hyde, A. L., Gangl, M. R., Mair, W. B., & Lee, C.-H. (2015). Hepatic Bmal1 Regulates Rhythmic Mitochondrial Dynamics and Promotes Metabolic Fitness. Cell Metabolism. https://doi.org/10.1016/j.cmet.2015.08.006
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