Quantitative Acetylomics Reveals Substrates of Lysine Acetyltransferase GCN5 in Adult and Aging Drosophila

Protein lysine acetylation is a dynamicpost-translationalmodification(PTM) that regulates a wide spectrum of cellular events includingaging. General control nonderepressible 5 (GCN5) is a highly conservedlysine acetyltransferase (KAT). However, the acetylation substratesof GCN5 in vivo remain poorly studied, and moreover, how lysine acetylationchanges with age and the contribution of KATs to aging remain to beaddressed. Here, using Drosophila, we perform label-freequantitative acetylomic analysis, identifying new substrates of GCN5in the adult and aging process. We further characterize the dynamicsof protein acetylation with age, which exhibits a trend of increase.Since the expression of endogenous fly Gcn5 progressivelyincreases during aging, we reason that, by combining the substrateanalysis, the increase in acetylation with age is triggered, at leastin part, by GCN5. Collectively, our study substantially expands theatlas of GCN5 substrates in vivo, provides a resource of protein acetylationthat naturally occurs with age, and demonstrates how individual KATcontributes to the aging acetylome.

Automated summary

Protein lysine acetylation is a dynamic PTM that regulates various cellular events, including aging. This study focuses on GCN5 and explores its acetylation substrates in vivo using Drosophila. The results reveal an increase in protein acetylation with age, potentially triggered by the progressive increase in endogenous fly Gcn5 expression. Overall, this study expands our understanding of GCN5 substrates and their contribution to the aging acetylome.