@article{a97deb0b588940dbb9ad5da80f7b6f5c,
title = "Reciprocal regulation of chaperone-mediated autophagy and the circadian clock",
abstract = "Circadian rhythms align physiological functions with the light–dark cycle through oscillatory changes in the abundance of proteins in the clock transcriptional programme. Timely removal of these proteins by different proteolytic systems is essential to circadian strength and adaptability. Here we show a functional interplay between the circadian clock and chaperone-mediated autophagy (CMA), whereby CMA contributes to the rhythmic removal of clock machinery proteins (selective chronophagy) and to the circadian remodelling of a subset of the cellular proteome. Disruption of this autophagic pathway in vivo leads to temporal shifts and amplitude changes of the clock-dependent transcriptional waves and fragmented circadian patterns, resembling those in sleep disorders and ageing. Conversely, loss of the circadian clock abolishes the rhythmicity of CMA, leading to pronounced changes in the CMA-dependent cellular proteome. Disruption of this circadian clock/CMA axis may be responsible for both pathways malfunctioning in ageing and for the subsequently pronounced proteostasis defect.",
author = "Juste, {Yves R.} and Susmita Kaushik and Mathieu Bourdenx and Ranee Aflakpui and Sanmay Bandyopadhyay and Fernando Garcia and Antonio Diaz and Kristen Lindenau and Vincent Tu and Krause, {Gregory J.} and Maryam Jafari and Rajat Singh and Javier Mu{\~n}oz and Fernando Macian and Cuervo, {Ana Maria}",
note = "Funding Information: We thank S. Tiano for excellent technical support with animal maintenance and biochemical procedures, J. Madrigal-Matute for early assistance in the analysis of the lysoproteome, and the Analytical Image and Animal Physiology Cores of the Albert Einstein College of Medicine for assistance with image acquisition and analysis and metabolic behaviour measurements. Circadian running wheel procedures were performed with assistance from The Neurobehavior Testing Core at UPenn/ITMAT and Intellectual and IDDRC at CHOP/Penn. This work was supported by grants from the National Institutes of Health (NIH) AG021904, AG054108, DK098408 (to A.M.C.), RF1AG043517 (to R.S.), AG031782 (to A.M.C., R.S. and F.M.) and the generous support of the Rainwaters Foundation and the JPB Foundation (to A.M.C.), the Glenn Foundation (to A.M.C. and F.M.), the Ikerbasque, Basque Foundation for Science, Bilbao, Spain (to J.M.) and U54 HD086984 (U Penn/IDDRC core) and AG038072 (Einstein Animal Physiology Core). Y.R.J. was supported by NIH training grant T32GM007491, G.J.K. by NIH training grants T32GM007288 and T32GM007491, and M.J. by NIH training grant T32HL14445. The CNIO Proteomics Unit lab is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013–2016, funded by ISCIII and ERDF. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = dec,
doi = "10.1038/s41556-021-00800-z",
language = "English (US)",
volume = "23",
pages = "1255--1270",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "12",
}