title: Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins.
abstract: Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied MS-based quantitative proteomics on isolated mitochondria from mice killed throughout the day and identified extensive oscillations in the mitochondrial proteome. Remarkably, the majority of cycling mitochondrial proteins peaked during the early light phase. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or on a high-fat diet. We propose that PERIOD proteins optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby, serve as a rheostat for mitochondrial nutrient utilization.
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Adi
authors: A
authors: Neufeld-Cohen
authors: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; robles@biochem.mpg.de gad.asher@weizmann.ac.il.
authors: Maria S
authors: MS
authors: Robles
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Rona
authors: R
authors: Aviram
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Gal
authors: G
authors: Manella
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Yaarit
authors: Y
authors: Adamovich
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Benjamin
authors: B
authors: Ladeuix
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Dana
authors: D
authors: Nir
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Liat
authors: L
authors: Rousso-Noori
authors: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors: Yael
authors: Y
authors: Kuperman
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel;
authors: Marina
authors: M
authors: Golik
authors: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany;
authors: Matthias
authors: M
authors: Mann
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel; robles@biochem.mpg.de gad.asher@weizmann.ac.il.
authors: Gad
authors: G
authors: Asher
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D002952:Citric Acid Cycle; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000378:metabolism; D004579:Electron Transport; D005227:Fatty Acids / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000201:enzymology / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009043:Motor Activity; D056950:Period Circadian Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020543:Proteome; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D024101:Mitochondrial Proteins; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D020543:Proteome; D012333:RNA, Messenger
keywords: PERIOD proteins; circadian rhythm; metabolism; mitochondria; proteomics