Diurnal Rhythms Spatially and Temporally Organize Autophagy

Mikhail Ryzhikov, Anna Ehlers, Deborah Steinberg, Wenfang Xie, Eitan Oberlander, Samuel Brown, Petra E. Gilmore, Reid R. Townsend, William S. Lane, Tamas Dolinay, Kiichi Nakahira, Augustine M.K. Choi, Jeffrey A. Haspel

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Circadian rhythms are a hallmark of physiology, but how such daily rhythms organize cellular catabolism is poorly understood. Here, we used proteomics to map daily oscillations in autophagic flux in mouse liver and related these rhythms to proteasome activity. We also explored how systemic inflammation affects the temporal structure of autophagy. Our data identified a globally harmonized rhythm for basal macroautophagy, chaperone-mediated autophagy, and proteasomal activity, which concentrates liver proteolysis during the daytime. Basal autophagy rhythms could be resolved into two antiphase clusters that were distinguished by the subcellular location of targeted proteins. Inflammation induced by lipopolysaccharide reprogrammed autophagic flux away from a temporal pattern that favors cytosolic targets and toward the turnover of mitochondrial targets. Our data detail how daily biological rhythms connect the temporal, spatial, and metabolic aspects of protein catabolism.

Original languageEnglish
Pages (from-to)1880-1892.e6
JournalCell Reports
Volume26
Issue number7
DOIs
StatePublished - Feb 12 2019

Keywords

  • autophagy
  • chaperone-mediated autophagy
  • circadian rhythm
  • clock
  • endotoxin
  • inflammation
  • lipopolysaccharide
  • macroautophagy
  • proteasome

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