Reciprocal regulation of chaperone-mediated autophagy and the circadian clock.
Nat Cell Biol
; 23(12): 1255-1270, 2021 12.
Article
em En
| MEDLINE
| ID: mdl-34876687
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ritmo Circadiano
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Proteína 2 de Membrana Associada ao Lisossomo
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Proteínas CLOCK
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Fatores de Transcrição ARNTL
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Relógios Circadianos
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Autofagia Mediada por Chaperonas
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article