Cell
Volume 146, Issue 4, 19 August 2011, Pages 607-620
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Article
Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival

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Summary

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.

Highlights

► N-alpha-acetylation of caspase-2 is required for binding to RAIDD during apoptosis ► Protein N-alpha-acetylation is sensitive to acetyl-CoA availability ► Acetyl-CoA levels are reduced in Bcl-xL-expressing cells ► The ability of Bcl-xL to reduce acetyl-CoA levels contributes to apoptotic resistance

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These authors contributed equally to this work