Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.
Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.
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DOI：
10.4161/auto.28919
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发表时间：
2014-07
期刊：
影响因子：
13.3
通讯作者：
Madeo F
中科院分区：
文献类型：
--
作者：
Schroeder S;Pendl T;Zimmermann A;Eisenberg T;Carmona-Gutierrez D;Ruckenstuhl C;Mariño G;Pietrocola F;Harger A;Magnes C;Sinner F;Pieber TR;Dengjel J;Sigrist SJ;Kroemer G;Madeo F
作为主要的溶酶体降解途径，自噬是细胞稳态的守护者，在饥饿条件下清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，自噬在衰老过程和相关病理中起着至关重要的作用。尽管自噬的调节很大程度上依赖于营养可利用性，但对调节自噬反应的特定代谢物的描述很少。最近，我们发现核胞浆乙酰辅酶A （AcCoA）是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，这就解释了为什么药理学或遗传操作可以改变核细胞质AcCoA的浓度，直接影响蛋白质乙酰化的水平。在酵母和哺乳动物细胞中，组蛋白和细胞质蛋白的乙酰化分别与自噬率呈负相关，尽管不同门的AcCoA合成途径不同。因此，我们提出核胞质AcCoA作为一种保守的代谢变阻器，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。
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.