1. Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival
- Author
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Yi, Caroline H., Pan, Heling, Seebacher, Jan, Jang, Il-Ho, Hyberts, Sven G., Heffron, Gregory J., Vander Heiden, Matthew G., Yang, Renliang, Li, Fupeng, Locasale, Jason W., Sharfi, Hadar, Zhai, Bo, Rodriguez-Mias, Ricard, Luithardt, Harry, Cantley, Lewis C., Daley, George Q., Asara, John M., Gygi, Steven P., Wagner, Gerhard, and Liu, Chuan-Fa
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METABOLIC regulation , *PROTEINS , *ACETYLATION , *APOPTOSIS , *CELLULAR signal transduction , *BIOLOGICAL assay , *MITOCHONDRIA , *GENE expression - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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