MAMMALIAN BAX TRIGGERS APOPTOTIC CHANGES IN YEAST

Apoptosis is co-regulated by the conserved family of Bcl-2-related pro teins, which includes both its agonists (Bax) and antagonists (Bcl-X-L ), A mutant strain of the yeast Saccharomyces cerevisiae has been show n to express all morphological signs of apoptosis. Overexpression of B ar is lethal in S. cerevisiae, whereas simultaneous overexpression of Bcl-X-L rescues the cells. We report that overexpression of mammalian Bar 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 bl ebbing, chromatin condensation and margination, and DNA fragmentation, Simultaneous overexpression of Bcl-X-L prevents these changes, We dem onstrate that Bar triggers phenotypic alterations in yeast strongly re sembling those it causes in metazoan apoptotic cells, (C) 1998 Federat ion of European Biochemical Societies.