Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins
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Significance: Mitochondria are major cellular energy suppliers and have to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. We obtained the first, to our knowledge, comprehensive mitochondrial proteome around the clock and identified extensive oscillations in mitochondrial protein abundance that predominantly peak during the early light phase. Remarkably, several rate-limiting mitochondrial enzymes that process different nutrients accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. Concurrently, we uncovered daily oscillations in mitochondrial respiration that are substrate-specific and peak during different times of the day. We propose that the circadian clock PERIOD proteins regulate the diurnal utilization of different nutrients by the mitochondria and thus, optimize mitochondrial function to daily changes in energy supply/demand.
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Elements of the molecular circadian clock directly regulate cellular metabolism and mitochondrial function in the liver and other tissues.
“Recent studies have demonstrated that elements of the molecular circadian clock directly regulate cellular metabolism and mitochondrial function in the liver and other tissues316–318.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [316]
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- Authors
- Neufeld-Cohen, A., Robles, M. S., Aviram, R., Manella, G., Adamovich, Y., Ladeuix, B., Nir, D., Rousso-Noori, L., Kuperman, Y., Golik, M., Mann, M., & Asher, G.
- Affiliations
- Weizmann Institute of Science (IL)
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried 82152, Germany;
- Max Planck Institute of Biochemistry (DE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-02-09
- Volume
- 113
- Issue
- 12
- Pages
- E1673-82
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4812734
- OpenAlex
- W2263654516
- Cited by
- 262
- References
- 54
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 26 · 2023: 24 · 2022: 25 · 2021: 25 · 2020: 20 · 2019: 20 · 2018: 30 · 2017: 21 · 2016: 21
- FWCI
- 19.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Research Consortium for Informatics and Mathematics (ERCIM) (ERC-2011 METACYCLES 310320)
- Israel Science Foundation (ISF 138/12)
- Human Frontier Science Program (HFSP CDA00014/2012)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- circadian clock, mitochondrial proteome, diurnal variation, mitochondrial respiration, rate-limiting enzyme, lipid metabolism, carbohydrate metabolism, nutrient utilization, energy metabolism, high-fat diet, clock proteins
- MeSH terms
- Animals, Circadian Rhythm, Citric Acid Cycle, Dietary Fats, Electron Transport, Fatty Acids, Feeding Behavior, Male, Mitochondria, Liver, Motor Activity, RNA, Messenger, Mice, Knockout, Proteome, Gene Expression Profiling, Mitochondrial Proteins, Mice, Period Circadian Proteins, Diet, High-Fat
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