期刊
MOLECULAR CELL
卷 53, 期 5, 页码 710-725出版社
CELL PRESS
DOI: 10.1016/j.molcel.2014.01.016
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资金
- Ligue Nationale contre le Cancer (Equipe labellisee)
- Agence Nationale pour la Recherche (ANR)
- Association pour la Recherche sur le Cancer
- European Research Council
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer
- Canceropole Ile-de-France
- Fondation Bettencourt-Schueller
- LabEx Onco-Immunology
- Paris Alliance of Cancer Research Institutes
- FRM
- Higher Education Commission (HEC) of Pakistan
- APART fellowship of the Austrian Academy of Sciences
- Ministerio de Economia y Competitividad (MINECO)
- Instituto de Salud Carlos III (RTICC)
- Botin Foundation
- FWF grants [LIPOTOX, P23490-B12, P24381-B20]
- Austrian Science Fund (FWF) [P 23490] Funding Source: researchfish
- Austrian Science Fund (FWF) [P23490] Funding Source: Austrian Science Fund (FWF)
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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