Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival.
Previous experiments suggest a connection between the N-alpha-acetylation of proteins and sensitivity of cells to apoptotic signals. Here, we describe a biochemical assay to detect the acetylation status of proteins and demonstrate that protein N-alpha-acetylation is regulated by the availability of acetyl-CoA. Because the antiapoptotic protein Bcl-xL is known to influence mitochondrial metabolism, we reasoned that Bcl-xL may provide a link between protein N-alpha-acetylation and apoptosis. Indeed, Bcl-xL overexpression leads to a reduction in levels of acetyl-CoA and N-alpha-acetylated proteins in the cell. This effect is independent of Bax and Bak, the known binding partners of Bcl-xL. Increasing cellular levels of acetyl-CoA by addition of acetate or citrate restores protein N-alpha-acetylation in Bcl-xL-expressing cells and confers sensitivity to apoptotic stimuli. We propose that acetyl-CoA serves as a signaling molecule that couples apoptotic sensitivity to metabolism by regulating protein N-alpha-acetylation.
Yi, CH; Pan, H; Seebacher, J; Jang, I-H; Hyberts, SG; Heffron, GJ; Vander Heiden, MG; Yang, R; Li, F; Locasale, JW; Sharfi, H; Zhai, B; Rodriguez-Mias, R; Luithardt, H; Cantley, LC; Daley, GQ; Asara, JM; Gygi, SP; Wagner, G; Liu, C-F; Yuan, J
Volume / Issue
Start / End Page
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)