Reciprocal regulation of chaperone-mediated autophagy and the circadian clock

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1255-1270
Number of pages16
JournalNature Cell Biology
Volume23
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Cell Biology

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