GCN5 acetyltransferase in cellular energetic and metabolic processes

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-1 alpha, a transcriptional coactivator that controls genes linked to energy metabolism and mitochondrial biogenesis. PGC-1 alpha 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-1 alpha acetylation across different tissues.

Automated summary

GCN5, encoded by the mammalian gene Kat2a, is a histone acetyltransferase that plays a crucial role in regulating gene expression programs in response to cellular metabolic and energetic states. It functions as a nutrient sensor, linking histone acetylation to transcriptional activation, and also plays a significant role in energy metabolism by acetylating proteins like PGC-1 alpha.