Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1

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http://hdl.handle.net/10138/304178

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Toledo , M , Batista-Gonzalez , A , Merheb , E , Aoun , M L , Tarabra , E , Feng , D , Sarparanta , J , Merlo , P , Botre , F , Schwartz , G J , Pessin , J E & Singh , R 2018 , ' Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 ' , Cell Metabolism , vol. 28 , no. 2 , pp. 268-+ . https://doi.org/10.1016/j.cmet.2018.05.023

Title: Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1
Author: Toledo, Miriam; Batista-Gonzalez, Ana; Merheb, Emilio; Aoun, Marie Louise; Tarabra, Elena; Feng, Daorong; Sarparanta, Jaakko; Merlo, Paola; Botre, Francesco; Schwartz, Gary J.; Pessin, Jeffrey E.; Singh, Rajat
Contributor: University of Helsinki, Genetics
Date: 2018-08-07
Language: eng
Number of pages: 18
Belongs to series: Cell Metabolism
ISSN: 1550-4131
URI: http://hdl.handle.net/10138/304178
Abstract: The circadian clock coordinates behavioral and circadian cues with availability and utilization of nutrients. Proteasomal degradation of clock repressors, such as cryptochrome (CRY) 1, maintains periodicity. Whether macroautophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERB alpha, and CRY1 are lysosomal targets, and that macroautophagy affects the circadian clock by selectively degrading CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that CRY1 degradation is timeimprinted to maintenance of blood glucose. High-fat feeding accelerates autophagic CRY1 degradation and contributes to obesity-associated hyperglycemia. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins with the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian glycemic control by regulating CRY1 degradation, revealing LIRs as potential targets for controlling hyperglycemia.
Subject: MAMMALIAN CIRCADIAN CLOCK
HEPATIC GLUCONEOGENESIS
RAT-LIVER
REV-ERB
TRANSCRIPTION
CRYPTOCHROME
PROTEINS
DEGRADATION
REVEALS
PERIOD
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
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