昼夜节律
生物钟
蛋白质稳态
生物
细胞生物学
自噬
蛋白质组
细菌昼夜节律
神经科学
遗传学
细胞凋亡
作者
Yves R. Juste,Susmita Kaushik,Mathieu Bourdenx,Ranee Aflakpui,Souvik Bandyopadhyay,Fernando Garcı́a,Antonio Díaz,Kristen Lindenau,Vincent Tu,Gregory J. Krause,Maryam Jafari,Rajat Singh,Javier Muñoz,Fernando Macián,Ana María Cuervo
标识
DOI:10.1038/s41556-021-00800-z
摘要
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. Juste, Kaushik and co-workers show that the circadian regulation of chaperone-mediated autophagy orchestrates the degradation of clock components and contributes to the circadian remodelling of the proteome.
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