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.
Ligr
M
M
Institut für Biochemie, Universität Stuttgart, Germany.
Madeo
F
F
Fröhlich
E
E
Hilt
W
W
Fröhlich
K U
KU
Wolf
D H
DH
D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation; D018014:Gene Transfer Techniques; D020287:In Situ Nick-End Labeling; D007211:Indoles; D008322:Mammals / Q000235:genetics; D008854:Microscopy, Electron; D010718:Phosphatidylserines / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D002843:Chromatin; D007211:Indoles; D010718:Phosphatidylserines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C007293:DAPI