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Regulation of Autophagy by Cytosolic Acetyl-Coenzyme A
Open accessAbstract
Acetyl-coenzyme A (AcCoA) is a major integrator of the nutritional status at the crossroads of fat, sugar, and protein catabolism. Here we show that nutrient starvation causes rapid depletion of AcCoA. AcCoA depletion entailed the commensurate reduction in the overall acetylation of cytoplasmic proteins, as well as the induction of autophagy, a homeostatic process of self-digestion. Multiple distinct manipulations designed to increase or reduce cytosolic AcCoA led to the suppression or induction of autophagy, respectively, both in cultured human cells and in mice. Moreover, maintenance of high AcCoA levels inhibited maladaptive autophagy in a model of cardiac pressure overload. Depletion of AcCoA reduced the activity of the acetyltransferase EP300, and EP300 was required for the suppression of autophagy by high AcCoA levels. Altogether, our results indicate that cytosolic AcCoA functions as a central metabolic regulator of autophagy, thus delineating AcCoA-centered pharmacological strategies that allow for the therapeutic manipulation of autophagy.
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“In fact, acetyl-CoA controls longevity and autophagy in a panel of model systems (Eisenberg et al., 2014; Mariño et al., 2014): This energy metabolite integrates various nutrition pathways and is the only known donor in acetylation reactions.”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Mariño et al., 2014
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Metadata
- Authors
- Mariño, G., Pietrocola, F., Eisenberg, T., Kong, Y., Malik, S. A., Andryushkova, A., Schroeder, S., Pendl, T., Harger, A., Niso-Santano, M., Zamzami, N., Scoazec, M., Durand, S., Enot, D. P., Fernández, Á. F., Martins, I., Kepp, O., Senovilla, L., Bauvy, C., Morselli, E., Vacchelli, E., Bennetzen, M., Magnes, C., Sinner, F., Pieber, T., López-Otín, C., Maiuri, M. C., Codogno, P., Andersen, J. S., Hill, J. A., Madeo, F., & Kroemer, G.
- Affiliations
- Inserm (FR)
- University of Graz (AT)
- The University of Texas Southwestern Medical Center (US)
- Joanneum Research (AT)
- Universidad de Oviedo (ES)
- University of Southern Denmark (DK)
- Corresponding author
- Madeo, Frank
- Kroemer, Guido
- ORCID
- Mariño, Guillermo
- Pietrocola, Federico
- Eisenberg, Tobias
- Malik, Shoaib Ahmad
- Pendl, Tobias
- Fernández, Álvaro F.
- Martins, Isabelle
- Kepp, Oliver
- Senovilla, Laura
- Morselli, Eugenia
- Vacchelli, Erika
- Magnes, Christoph
- Sinner, Frank
- Pieber, Thomas
- Maiuri, Maria Chiara
- Codogno, Patrice
- Andersen, Jens S.
- Hill, Joseph A.
- Madeo, Frank
- Kroemer, Guido
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 53
- Issue
- 5
- Pages
- 710-725
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2095000965
- Cited by
- 500
- References
- 53
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 33 · 2023: 32 · 2022: 41 · 2021: 52 · 2020: 51 · 2019: 54 · 2018: 50 · 2017: 34 · 2016: 39 · 2015: 39 · 2014: 28
- FWCI
- 35.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Extremadura (University of Extremadura) (submittedVersion, other-oa)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-PHUC-0002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- acetyl-CoA, autophagy regulation, protein acetylation, nutrient deprivation, EP300, acetyltransferase, cardiac pressure overload, metabolic regulation, autophagy induction, autophagy inhibition
- MeSH terms
- Acetyl Coenzyme A, Adenosine Triphosphate, Animals, Autophagy, Cell Nucleus, Cytoplasm, Cytosol, HeLa Cells, Humans, Ketoglutaric Acids, Mice, Inbred C57BL, Microscopy, Fluorescence, Mitochondria, Gene Expression Regulation, Enzymologic, RNA, Small Interfering, HCT116 Cells, Cell Line, Tumor, Green Fluorescent Proteins, E1A-Associated p300 Protein, Mice
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