乙酰辅酶 A：自噬和长寿的代谢主要调节剂。,Autophagy

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乙酰辅酶 A：自噬和长寿的代谢主要调节剂。
Autophagy ( IF 14.6 ) Pub Date : 2014-06-07 , DOI: 10.4161/auto.28919
Sabrina Schroeder ₁ , Tobias Pendl ₁ , Andreas Zimmermann ₁ , Tobias Eisenberg ₁ , Didac Carmona-Gutierrez ₁ , Christoph Ruckenstuhl ₁ , Guillermo Mariño ₂ , Federico Pietrocola ₂ , Alexandra Harger ₃ , Christoph Magnes ₄ , Frank Sinner ₅ , Thomas R Pieber ₅ , Jörn Dengjel ₆ , Stephan J Sigrist ₇ , Guido Kroemer ₈ , Frank Madeo ₁

Affiliation

Institute of Molecular Biosciences; University of Graz; Graz, Austria.
INSERM U848; Pavillon de Recherche 1; Villejuif, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Pavillon de Recherche 1; Villejuif, France; Université Paris Sud; Faculté de Médecine; Le Kremlin Bicêtre; France.
Institute of Molecular Biosciences; University of Graz; Graz, Austria; Division of Endocrinology and Metabolism; Dept. of Internal Medicine; Medical University of Graz; Graz, Austria.
HEALTH-Institute for Biomedicine and Health Sciences; Joanneum Research Forschungsgesellschaft m.b.H.; Graz, Austria.
Division of Endocrinology and Metabolism; Dept. of Internal Medicine; Medical University of Graz; Graz, Austria; HEALTH-Institute for Biomedicine and Health Sciences; Joanneum Research Forschungsgesellschaft m.b.H.; Graz, Austria.
Department of Dermatology; University Freiburg Medical Center; Freiburg, Germany.
Institute for Biology/Genetics; Freie Universität; Berlin, Germany; NeuroCure; Charité; Berlin, Germany.
INSERM U848; Pavillon de Recherche 1; Villejuif, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Pavillon de Recherche 1; Villejuif, France; Université Paris Sud; Faculté de Médecine; Le Kremlin Bicêtre; France; Equipe 11 labellisée Ligue contre le cancer; INSERM U1138; Centre de Recherche des Cordeliers; Paris, France; Pôle de Biologie; Hôpital Européen Georges Pompidou; AP-HP; Paris, France; Université Paris Descartes; Sorbonne Paris Cité; Paris, France.

作为主要的溶酶体降解途径，自噬代表了细胞稳态的守护者，在饥饿条件下去除受损和潜在有害物质并补充能量储备。鉴于其巨大的生理重要性，自噬在衰老和相关病理过程中起着至关重要的作用。尽管自噬的调节在很大程度上取决于营养物质的可用性，但调节自噬反应的特定代谢物的描述却很少。最近，我们发现核胞质乙酰辅酶 A (AcCoA) 作为一种系统发育保守的饥饿诱导和年龄相关自噬抑制剂。AcCoA 是蛋白质乙酰化的唯一乙酰基供体，解释了为什么改变核细胞溶质 AcCoA 浓度的药理学或遗传操作直接影响蛋白质乙酰化水平。组蛋白和胞质蛋白的乙酰化分别与酵母和哺乳动物细胞中的自噬率呈负相关，尽管从头合成 AcCoA 的途径在不同门中有所不同。因此，我们提出核-胞质 AcCoA 作为保守的代谢变阻器，通过对蛋白质乙酰化的影响将细胞代谢状态与自噬调节联系起来。

"点击查看英文标题和摘要"

Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.

As the major lysosomal degradation pathway, autophagy represents the guardian of cellular homeostasis, removing damaged and potentially harmful material and replenishing energy reserves in conditions of starvation. Given its vast physiological importance, autophagy is crucially involved in the process of aging and associated pathologies. Although the regulation of autophagy strongly depends on nutrient availability, specific metabolites that modulate autophagic responses are poorly described. Recently, we revealed nucleo-cytosolic acetyl-coenzyme A (AcCoA) as a phylogenetically conserved inhibitor of starvation-induced and age-associated autophagy. AcCoA is the sole acetyl-group donor for protein acetylation, explaining why pharmacological or genetic manipulations that modify the concentrations of nucleo-cytosolic AcCoA directly affect the levels of protein acetylation. The acetylation of histones and cytosolic proteins inversely correlates with the rate of autophagy in yeast and mammalian cells, respectively, despite the fact that the routes of de novo AcCoA synthesis differ across phyla. Thus, we propose nucleo-cytosolic AcCoA to act as a conserved metabolic rheostat, linking the cellular metabolic state to the regulation of autophagy via effects on protein acetylation.

更新日期：2014-05-15

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