Reciprocal regulation of chaperone-mediated autophagy and the circadian clock

© 2021. The Author(s), under exclusive licence to Springer Nature Limited..

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.

Errataetall:

CommentIn: Nat Cell Biol. 2021 Dec;23(12):1220-1221. - PMID 34876686

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Nature cell biology - 23(2021), 12 vom: 17. Dez., Seite 1255-1270

Sprache:

Englisch

Beteiligte Personen:

Juste, Yves R [VerfasserIn]
Kaushik, Susmita [VerfasserIn]
Bourdenx, Mathieu [VerfasserIn]
Aflakpui, Ranee [VerfasserIn]
Bandyopadhyay, Sanmay [VerfasserIn]
Garcia, Fernando [VerfasserIn]
Diaz, Antonio [VerfasserIn]
Lindenau, Kristen [VerfasserIn]
Tu, Vincent [VerfasserIn]
Krause, Gregory J [VerfasserIn]
Jafari, Maryam [VerfasserIn]
Singh, Rajat [VerfasserIn]
Muñoz, Javier [VerfasserIn]
Macian, Fernando [VerfasserIn]
Cuervo, Ana Maria [VerfasserIn]

Links:

Volltext

Themen:

ARNTL Transcription Factors
Bmal1 protein, mouse
CLOCK Proteins
EC 2.3.1.48
Journal Article
Lysosomal-Associated Membrane Protein 2
Proteome
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.02.2022

Date Revised 13.12.2023

published: Print-Electronic

CommentIn: Nat Cell Biol. 2021 Dec;23(12):1220-1221. - PMID 34876686

Citation Status MEDLINE

doi:

10.1038/s41556-021-00800-z

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334133211