General Control Non-repressed 5 protein (GCN5), encoded by the mammalian gene Kat2a, is the first histone acetyltransferase discovered to link histone acetylation to transcriptional activation [1]. The enzymatic activity of GCN5 is linked to cellular metabolic and energetic states regulating gene expression programs. GCN5 has a major impact on energy metabolism by i) sensing acetyl-CoA, a central metabolite and substrate of the GCN5 catalytic reaction, and ii) acetylating proteins such as PGC-1α, a transcriptional coactivator that controls genes linked to energy metabolism and mitochondrial biogenesis. PGC-1α is biochemically associated with the GCN5 protein complex during active metabolic reprogramming. In the first part of the review, we examine how metabolism can change GCN5-dependent histone acetylation to regulate gene expression to adapt cells. In the second part, we summarize the GCN5 function as a nutrient sensor, focusing on non-histone protein acetylation, mainly the metabolic role of PGC-1α acetylation across different tissues.

一般控制非抑制 5 蛋白 (GCN5) 由哺乳动物基因Kat2a编码，是第一个被发现将组蛋白乙酰化与转录激活联系起来的组蛋白乙酰转移酶 [1]。 GCN5 的酶活性与调节基因表达程序的细胞代谢和能量状态有关。 GCN5 通过 i) 感应乙酰辅酶 A（GCN5 催化反应的中心代谢物和底物）和 ii) 乙酰化蛋白质（例如 PGC-1α）（一种转录共激活因子，控制与能量代谢和线粒体相关的基因）对能量代谢产生重大影响。生物发生。 PGC-1α 在活性代谢重编程过程中与 GCN5 蛋白复合物发生生化相关。在综述的第一部分中，我们研究了代谢如何改变 GCN5 依赖性组蛋白乙酰化来调节基因表达以适应细胞。在第二部分中，我们总结了GCN5作为营养传感器的功能，重点关注非组蛋白乙酰化，主要是PGC-1α乙酰化跨不同组织的代谢作用。