Activation of a set of proteases known as caspases is an important part of the cellular signaling mechanisms that lead to cell death or apoptosis. One caspase target is the protein BID, which, after cleavage, translocates from the cytosol to the mitochondrial membrane. There, it interacts with other proteins to influence mitochondrial function and the release of cytochrome c. Zha et al. now provide a surprising mechanism for how cleavage of BID results in mitochondrial targeting. Cleavage of BID exposes an NH2-terminal glycine residue, which then undergoes a lipid modification (myristoylation) that enhances its binding to mitochondrial membranes. Furthermore, a mutant that cannot be myristoylated has reduced apoptotic activity. Previously, myristoylation of mammalian proteins has only been observed as a cotranslational modification. Myristoylation may be acutely regulated and may serve as a switch that alters localization of signaling proteins.
Zha, J., Weiler, S., Oh, K.J., Wei, M.C., and Korsmeyer, S.J. (2000) Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis. Science 290: 1761-1765. [Abstract] [Full Text]