@article{fe29a4a5b61b4c02b0e44eb12fe03fe7,
title = "Diurnal Rhythms Spatially and Temporally Organize Autophagy",
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.",
keywords = "autophagy, chaperone-mediated autophagy, circadian rhythm, clock, endotoxin, inflammation, lipopolysaccharide, macroautophagy, proteasome",
author = "Mikhail Ryzhikov and Anna Ehlers and Deborah Steinberg and Wenfang Xie and Eitan Oberlander and Samuel Brown and Gilmore, {Petra E.} and Townsend, {Reid R.} and Lane, {William S.} and Tamas Dolinay and Kiichi Nakahira and Choi, {Augustine M.K.} and Haspel, {Jeffrey A.}",
note = "Funding Information: We thank Erik Herzog, Michael Hughes, Steven Brody, Amjad Horani, Robyn Haspel, Renee Robinson, John Neveu, and the Clocks & Sleep Club at the Hope Center for Neurological Disorders, Washington University School of Medicine, for their scientific input. This work was funded by K08GM102694, RO1HL135846, a Children's Development Institute grant ( PD-II-2016-529 ), ATS Recognition Award for Outstanding Early Career Investigators, VA ( VISN1 ) Career Development Award I, and a Parker B. Francis Scientific Opportunity Award (to J.A.H.). It was also funded by P01HL114501 and R01HL133801 (to A.M.K.C.) and T32HL007317 (to M.R.). Funding Information: We thank Erik Herzog, Michael Hughes, Steven Brody, Amjad Horani, Robyn Haspel, Renee Robinson, John Neveu, and the Clocks & Sleep Club at the Hope Center for Neurological Disorders, Washington University School of Medicine, for their scientific input. This work was funded by K08GM102694, RO1HL135846, a Children's Development Institute grant (PD-II-2016-529), ATS Recognition Award for Outstanding Early Career Investigators, VA (VISN1) Career Development Award I, and a Parker B. Francis Scientific Opportunity Award (to J.A.H.). It was also funded by P01HL114501 and R01HL133801 (to A.M.K.C.) and T32HL007317 (to M.R.). Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = feb,
day = "12",
doi = "10.1016/j.celrep.2019.01.072",
language = "English (US)",
volume = "26",
pages = "1880--1892.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}