Cryptochromes Suppress HIF1α in Muscles

IScience
Megan E VaughanKatja A Lamia

Abstract

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 (PPARδ), a major driver of oxidative metabolism and exercise endurance. CRY-deficient mice exhibit enhanced PPARδ 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 HIF1α-BMAL1 heterodimers. Furthermore, CRY2 appeared to be more effective than CRY1 in the reduction of HIF1α protein steady-state levels in primary myotubes and quadriceps in vivo. Finally, CRY-deficient myotubes exhibit metabolic alterations consistent with cryptochrome-dependent suppression of HIF1α, which likely contributes to circadian modulation of muscle metabolism.

References

May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·J B HogeneschC A Bradfield
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·M H VitaternaA Sancar
Apr 21, 2001·Molecular and Cellular Biology·T N SeagrovesR S Johnson
Jan 29, 2002·Biochemical and Biophysical Research Communications·Karen D Cowden, M Celeste Simon
May 23, 2002·Cell·Satchidananda PandaJohn B Hogenesch
Jan 15, 2003·Experimental Physiology·Hans HoppelerMartin Flück
Dec 4, 2003·The International Journal of Biochemistry & Cell Biology·Robyn J KewleyAnne Chapman-Smith
Aug 26, 2004·PLoS Biology·Steven D MasonRandall S Johnson
Dec 22, 2007·Expert Review of Anticancer Therapy·W Kimryn Rathmell, Shufen Chen
Feb 22, 2011·The Journal of Biological Chemistry·Ya-Min TianPeter J Ratcliffe
Jun 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nina ScheererJoachim Fandrey
Aug 7, 2013·Exercise and Sport Sciences Reviews·Elizabeth A Schroder, Karyn A Esser
Oct 9, 2013·Critical Reviews in Biochemistry and Molecular Biology·Veronica L DenglerJoaquín M Espinosa
Nov 23, 2013·Nature Reviews. Cancer·David C BerstenMurray L Whitelaw
Feb 26, 2014·Molecular Metabolism·Kenneth A DyarStefano Schiaffino
Apr 8, 2014·The International Journal of Biochemistry & Cell Biology·Laura TerraneoMichele Samaja
Dec 3, 2014·Molecular Cell·Nathaniel M VacantiChristian M Metallo
Aug 8, 2015·Nature·Dalei WuFraydoon Rastinejad
Sep 24, 2015·Experimental Physiology·Malene E Lindholm, Helene Rundqvist
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale
Jun 17, 2016·Molecular & Cellular Oncology·Adela DePaviaXian-De Liu
Oct 11, 2016·Current Opinion in Structural Biology·Dalei Wu, Fraydoon Rastinejad
Oct 25, 2016·Cell Metabolism·Yaarit AdamovichGad Asher
Nov 15, 2016·Molecular Cell·Anne-Laure HuberKatja A Lamia
Dec 19, 2016·Nature Reviews. Genetics·Joseph S Takahashi
May 17, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jennifer L Fribourgh, Carrie L Partch
Jun 18, 2017·Molecular Cell·Mircea Ivan, William G Kaelin
Jul 7, 2017·Cell Metabolism·Sabine D JordanKatja A Lamia
Jul 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Anna KriebsKatja A Lamia
Mar 21, 2018·Nature Communications·Clark RosensweigCarla B Green
Jun 26, 2018·Cell Metabolism·Miriam ToledoRajat Singh
Oct 18, 2018·Nature Chemical Biology·Martina WallaceChristian M Metallo

❮ Previous
Next ❯

Citations

Jun 24, 2021·Molecular Aspects of Medicine·Kenichiro KinouchiHiroshi Itoh
Jun 30, 2021·Proceedings of the National Academy of Sciences of the United States of America·Alanna B ChanKatja A Lamia
Jul 3, 2021·Diagnostics·Bala S C KoritalaDavid F Smith

❮ Previous
Next ❯

Methods Mentioned

BETA
two-hybrid
immunoprecipitation
PCR
co-immunoprecipitation
pull down
transfection

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.