Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1

Toledo, Míriam; Tarabra, Elena; Batista‐González, Ana; Merlo, Paola; Feng, Daorong; Sarparanta, J.; Botrè, Francesco; Pessin, Jeffrey E.; Singh, Rajat

doi:10.2139/ssrn.3155564

Cited by 30 publications

(37 citation statements)

References 48 publications

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“…The stimulation of AMPK destabilizes cryptochromes and alters CR, and mice in which the AMPK pathway is genetically disrupted show alterations in their peripheral clocks 72 . The circadian proteins BMAL1, CLOCK, REV-ERBα, and Cry1 are lysosomal targets, and the selective autophagic degradation of Cry1 occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that Cry1 degradation is time imprinted for the maintenance of blood glucose 75 . In addition, high-fat feeding accelerates autophagic Cry1 degradation and contributes to obesity-associated hyperglycemia 75 .…”

Section: Autophagy Regulates the Circadian Rhythmmentioning

confidence: 99%

“…The circadian proteins BMAL1, CLOCK, REV-ERBα, and Cry1 are lysosomal targets, and the selective autophagic degradation of Cry1 occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that Cry1 degradation is time imprinted for the maintenance of blood glucose 75 . In addition, high-fat feeding accelerates autophagic Cry1 degradation and contributes to obesity-associated hyperglycemia 75 . A CLOCK mutant attenuates BMAL1 degradation through both proteasomal and autophagic pathways under high-fat diet feeding, providing evidence of autophagic regulation of a core clock component 76 .…”

Section: Autophagy Regulates the Circadian Rhythmmentioning

confidence: 99%

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The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Zhang

Dong

et al. 2020

Exp Mol Med

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There is one circadian clock in the central nervous system and another in the peripheral organs, and the latter is driven by an autoregulatory molecular clock composed of several core clock genes. The height, water content, osmotic pressure and mechanical characteristics of intervertebral discs (IVDs) have been demonstrated to exhibit a circadian rhythm (CR). Recently, a molecular clock has been shown to exist in IVDs, abolition of which can lead to stress in nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IDD). Autophagy is a fundamental cellular process in eukaryotes and is essential for individual cells or organs to respond and adapt to changing environments; it has also been demonstrated to occur in human NPCs. Increasing evidence supports the hypothesis that autophagy is associated with CR. Thus, we review the connection between CR and autophagy and the roles of these mechanisms in IDD.

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Section: Autophagy Regulates the Circadian Rhythmmentioning

confidence: 99%

Section: Autophagy Regulates the Circadian Rhythmmentioning

confidence: 99%

The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Zhang

Dong

et al. 2020

Exp Mol Med

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“…Indeed, mice with diverse clock impairments develop hyperglycemia, hypoinsulinemia and glucose intolerance. When sleep or food intake occurs in desynchrony with the internal circadian time of the organism, a condition called "circadian misalignment", this leads to the development of metabolic disorders comprising obesity, fatty liver disease, diabetes, cardiovascular diseases, hypertension and cancer (right schema) 110,125,126 Moreover, CRY1 levels are decreased by autophagy in rodent liver, providing a link between autophagy, increased gluconeogenesis and the overall maintenance of glucose homeostasis. 30,109,[112][113][114][115][116][117][118][119][120] In skeletal muscle, REV-ERBα directly represses enzymes essential for lipid and protein metabolism, along with BMAL1, which activates key regulators of lipid metabolism.…”

Section: Of Mammalian Physiology and Metabolismmentioning

confidence: 99%

“…31,59,71,77,[107][108][109][110][111] The nuclear receptor REV-ERBα is a key regulator of lipid, carbohydrate and protein metabolism. 126 Furthermore, diet-induced obesity in wild-type mice causes remodelling of the circadian liver enhancer landscape, leading to massive changes in lipid metabolism via SREBP and PPARα. Indeed, muscle-specific loss of BMAL1 directly leads to metabolic inefficiency, impairs muscle triglyceride biosynthesis, and causes accumulation of bioactive lipids and amino acids in mice.…”

Section: Of Mammalian Physiology and Metabolismmentioning

confidence: 99%

The importance of being rhythmic: Living in harmony with your body clocks

Dibner

2019

Acta Physiologica

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OSCILLATORSThe time-keeping system, dubbed "circadian" from Latin circa diem (about a day), allows light-sensitive beings, including humans, to coordinate their physiology and behaviour to the daily changes in geophysical time (Figure 1). The mammalian network of body clocks is organized in a strictly hierarchical manner. A master oscillator, residing in the paired suprachiasmatic nuclei (SCN) of the hypothalamus ( Figure 1A), synchronizes a myriad of peripheral oscillators situated in each organ ( Figure 1B) on a daily basis. In turn, rhythmicity in the SCN is entrained by external timecues or Zeitgebers (German term for time givers). Daily changes in light intensity, detected by classical photoreceptors and intrinsically light-sensitive retinal ganglion cells expressing AbstractCircadian rhythms have developed in all light-sensitive organisms, including humans, as a fundamental anticipatory mechanism that enables proactive adaptation to environmental changes. The circadian system is organized in a highly hierarchical manner, with clocks operative in most cells of the body ensuring the temporal coordination of physiological processes. Circadian misalignment, stemming from modern life style, draws increasing attention due to its tight association with the development of metabolic, cardiovascular, inflammatory and mental diseases as well as cancer.This review highlights recent findings emphasizing the role of the circadian system in the temporal orchestration of physiology, with a particular focus on implications of circadian misalignment in human pathologies. K E Y W O R D Scircadian clock, circadian misalignment, continuous recording of circadian bioluminescence, human physiology How to cite this article: Dibner C. The importance of being rhythmic: Living in harmony with your body clocks. Acta Physiol. 2020;228:e13281. https ://doi.

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“…Activated AKT also regulates the transcription factor CLOCK, crucial circadian rhythm element controlling cell function, energy metabolism, immunity, glucose, and lipid, metabolism . CLOCK is controlled by the lysosome which is regulated by the phosphorylated and activated AKT that controls the development of cancer, metastasis and cancer relapse …”

Section: Lysosome Activates Akt Inducing Cancer Metastasis or Cancermentioning

confidence: 99%

Lysosome activates AKT inducing cancer and metastasis

Radisavljevic

2019

J of Cellular Biochemistry

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Hyperactivated lysosome causes cancer and induces metastasis or cancer relapse. Such activation occurs during excessive, intense, and protracted oxidative burst in the lysosome. The burst induces the formation of the constitutively active (permanently active) AKT locus generating cancer complexity and robustness. Such condition has the tendency to persist by stabilized intense signaling inducing upregulation of cell function and metabolic setup at the higher level. Most intense activator of the lysosome is the fungus Aspergillus fumigatus, which activates the AKT, a critical element in lysosome control, inducing cancer development, metastatic progression, or cancer relapse. Targeting the AKT active site of hydrogen network, by redox balance change or hydrogen balance change or muon-catalyzed fusion or laserinduced fusion with anti-A. fumigatus medication converts active AKT locus into inactive element, inducing disappearance of malignant phenotype.

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Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1

Abstract: Highlights d Core circadian proteins are temporally degraded by lysosomes d Loss of autophagy promotes CRY1 accumulation and disrupts the circadian clock d Autophagy drives gluconeogenesis by degrading CRY1 d LIR motifs link CRY1 degradation to regulation of glucose homeostasis

Cited by 30 publications

References 48 publications

The circadian rhythm in intervertebral disc degeneration: an autophagy connection

The circadian rhythm in intervertebral disc degeneration: an autophagy connection

The importance of being rhythmic: Living in harmony with your body clocks

Lysosome activates AKT inducing cancer and metastasis

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