Department of Cell Biology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Cell. 2011 Aug 19;146(4):607-20. doi: 10.1016/j.cell.2011.06.050.
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.
先前的实验表明蛋白质的 N-α-乙酰化与细胞对凋亡信号的敏感性之间存在关联。在这里，我们描述了一种生化检测方法来检测蛋白质的乙酰化状态，并证明蛋白质的 N-α-乙酰化受到乙酰辅酶 A 可用性的调节。由于已知抗凋亡蛋白 Bcl-xL 会影响线粒体代谢，我们推断 Bcl-xL 可能是蛋白质 N-α-乙酰化和凋亡之间的联系。事实上，Bcl-xL 的过表达会导致细胞内乙酰辅酶 A 和 N-α-乙酰化蛋白水平降低。这种效应独立于 Bax 和 Bak，它们是 Bcl-xL 的已知结合伴侣。通过添加乙酸盐或柠檬酸盐增加细胞内乙酰辅酶 A 的水平可恢复 Bcl-xL 表达细胞中的蛋白质 N-α-乙酰化，并使细胞对凋亡刺激敏感。我们提出乙酰辅酶 A 可作为一种信号分子，通过调节蛋白质 N-α-乙酰化将凋亡敏感性与代谢联系起来。
