puc-header

Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1

37 Pages Posted: 5 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Miriam Toledo

Miriam Toledo

Yeshiva University - Department of Medicine; Yeshiva University - Department of Molecular Pharmacology

Elena Tarabra

Yeshiva University - Department of Medicine

Ana Batista-Gonzalez

Yeshiva University - Department of Medicine; Yeshiva University - Department of Molecular Pharmacology

Paola Merlo

Italian Sports Medical Federation (FMSI) - Antidoping Laboratory

Daorong Feng

Yeshiva University - Department of Medicine

Jaakko Sarparanta

Yeshiva University - Department of Medicine; Yeshiva University - Department of Molecular Pharmacology

Francesco Botrè

Italian Sports Medical Federation (FMSI) - Antidoping Laboratory; University of Rome I - Department of Experimental Medicine

Jeffrey E. Pessin

Yeshiva University - Department of Medicine; Yeshiva University - Department of Molecular Pharmacology; Yeshiva University - Institute for Aging Research; Yeshiva University - Diabetes Research Center

Rajat Singh

Yeshiva University - Department of Medicine; Yeshiva University - Department of Molecular Pharmacology; Yeshiva University - Institute for Aging Research; Yeshiva University - Diabetes Research Center

More...

Abstract

The circadian clock coordinates behavioral and circadian cues with the availability and utilization of nutrients. Proteasomal degradation of clock repressors, e.g., cryptochrome (CRY)1 maintains periodicity of the clock. Whether autophagy, a quality control pathway, degrades circadian proteins remains unknown. Here we show that circadian proteins BMAL1, CLOCK, REV-ERB, and CRY1 are lysosomal targets, and that α macroautophagy (hereafter autophagy) specifically degrades CRY1. Autophagic degradation of CRY1, an inhibitor of gluconeogenesis, occurs in a diurnal window when rodents rely on gluconeogenesis, suggesting that degradation of CRY1 is time-imprinted to maintenance of blood glucose levels. CRY1 contains several light chain 3 (LC3)-interacting region (LIR) motifs, which facilitate the interaction of cargo proteins to the autophagosome marker LC3. Using mutational analyses, we identified two distinct LIRs on CRY1 that exert circadian control over blood glucose levels by regulating CRY1 degradation, revealing CRY1 LIRs as potential targets in regulation of glucose metabolism.

Suggested Citation

Toledo, Miriam and Tarabra, Elena and Batista-Gonzalez, Ana and Merlo, Paola and Feng, Daorong and Sarparanta, Jaakko and Botrè, Francesco and Pessin, Jeffrey E. and Singh, Rajat, Autophagy Regulates the Liver Clock and Glucose Metabolism by Degrading CRY1 (2018). Available at SSRN: https://ssrn.com/abstract=3155564 or http://dx.doi.org/10.2139/ssrn.3155564
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Miriam Toledo

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Department of Molecular Pharmacology

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Elena Tarabra

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Ana Batista-Gonzalez

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Department of Molecular Pharmacology

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Paola Merlo

Italian Sports Medical Federation (FMSI) - Antidoping Laboratory

Viale Tiziano, 70
00196 Roma RM
Italy

Daorong Feng

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Jaakko Sarparanta

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Department of Molecular Pharmacology

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Francesco Botrè

Italian Sports Medical Federation (FMSI) - Antidoping Laboratory

Viale Tiziano, 70
00196 Roma RM
Italy

University of Rome I - Department of Experimental Medicine

Piazzale Aldo Moro, 5
Rome, 00185
Italy

Jeffrey E. Pessin

Yeshiva University - Department of Medicine

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Department of Molecular Pharmacology

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Institute for Aging Research

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Diabetes Research Center

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Rajat Singh (Contact Author)

Yeshiva University - Department of Medicine ( email )

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Department of Molecular Pharmacology ( email )

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Institute for Aging Research ( email )

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Yeshiva University - Diabetes Research Center ( email )

Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Bronx, NY 10461
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
607
Downloads
23