title: Metabolic regulation of protein N-alpha-acetylation by Bcl-xL promotes cell survival.
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.
authors.affiliation: Department of Cell Biology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Yi
authors.forename: Heling
authors.initials: H
authors.lastname: Pan
authors.forename: Jan
authors.initials: J
authors.lastname: Seebacher
authors.forename: Il-Ho
authors.initials: IH
authors.lastname: Jang
authors.forename: Sven G
authors.initials: SG
authors.lastname: Hyberts
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Heffron
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Vander Heiden
authors.forename: Renliang
authors.initials: R
authors.lastname: Yang
authors.forename: Fupeng
authors.initials: F
authors.lastname: Li
authors.forename: Jason W
authors.initials: JW
authors.lastname: Locasale
authors.forename: Hadar
authors.initials: H
authors.lastname: Sharfi
authors.forename: Bo
authors.initials: B
authors.lastname: Zhai
authors.forename: Ricard
authors.initials: R
authors.lastname: Rodriguez-Mias
authors.forename: Harry
authors.initials: H
authors.lastname: Luithardt
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Cantley
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Chuan-Fa
authors.initials: CF
authors.lastname: Liu
authors.forename: Junying
authors.initials: J
authors.lastname: Yuan
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D053143:Caspase 2 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D011506:Proteins; D051020:bcl-X Protein; D053143:Caspase 2