Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival
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Yi-2011-Metabolic Regulation.pdf
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1.49 MB
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Author(s)
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.
Date Issued
August 2011
Journal
Cell
Publisher
Elsevier
Citation
Yi, Caroline H., Heling Pan, Jan Seebacher, Il-Ho Jang, Sven G. Hyberts, Gregory J. Heffron, Matthew G. Vander Heiden, et al. “Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes Cell Survival.” Cell 146, no. 4 (August 2011): 607–620. © 2011 Elsevier Inc.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.06.050
