Circadian remodeling of the proteome by chaperone-mediated autophagy

Research output: Contribution to journalComment/debatepeer-review

Abstract

The circadian clock drives daily cycles of physiology and behavioral outputs to keep organisms in tune with the environment. Cyclic oscillations in levels of the clock proteins maintain circadian rhythmicity. In our recent work, we have discovered the interdependence of the circadian clock and chaperone-mediated autophagy (CMA), a selective form of lysosomal protein degradation. Central and peripheral degradation of core clock proteins by CMA (selective chronophagy) modulates circadian rhythm. Loss of CMA in vivo disrupts physiological circadian cycling, resembling defects observed in aging, a condition with reduced CMA. Conversely, the circadian clock temporally regulates CMA activity in a tissue-specific manner, contributing to remodeling of a distinct subproteome at different circadian times. This timely remodeling cannot be sustained when CMA fails, despite rerouting of some CMA substrates to other degradation pathways.

Original languageEnglish (US)
JournalAutophagy
DOIs
StateAccepted/In press - 2022

Keywords

  • Central clock
  • chaperones
  • circadian rhythms
  • lysosomes
  • organelle proteomics
  • peripheral clock

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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