Mammalian Bax triggers apoptotic changes in yeast

Apoptosis is co-regulated by the conserved family of Bcl-2-related proteins, which includes both its agonists (Bax) and antagonists (Bcl-X L). A mutant strain of the yeast Saccharomyces cerevisiae has been shown to express all morphological signs of apoptosis. Overexpression of Bax is lethal in S. cerevisiae, whereas simultaneous overexpression of Bcl-X L rescues the cells. We report that overexpression of mammalian Bax in a S. cerevisiae wild type strain triggers morphological changes similar to those of apoptotic metazoan cells: the loss of asymmetric distribution of plasma membrane phosphatidylserine, plasma membrane blebbing, chromatin condensation and margination, and DNA fragmentation. Simultaneous overexpression of Bcl-X L prevents these changes. We demonstrate that Bax triggers phenotypic alterations in yeast strongly resembling those it causes in metazoan apoptotic cells.