Oxygen Stress: A Regulator of Apoptosis in Yeast

doi:10.1083/jcb.145.4.757

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© The Rockefeller University Press, 0021-9525/1999//757 $5.00
The Journal of Cell Biology, Volume 145, Number 4, , 1999 757-767

Regular Articles

Oxygen Stress: A Regulator of Apoptosis in Yeast

Frank Madeo^*, Eleonore Fröhlich, Martin Ligr, Martin Grey^||, Stephan J. Sigrist^¶, Dieter H. Wolf, and Kai-Uwe Fröhlich^*

^* Physiologisch-Chemisches Institut, Universität Tübingen, 72076 Tübingen, Germany; Anatomisches Institut, Universität Tübingen, 72074 Tübingen, Germany; Institut für Biochemie, Universität Stuttgart, 70569 Stuttgart, Germany; ^|| Johann Wolfgang Goethe-Universität, 60590 Frankfurt am Main, Germany; and ^¶ Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, 72076 Tübingen, Germany

Oxygen radicals are important components of metazoan apoptosis.We have found that apoptosis can be induced in the yeast Saccharomycescerevisiae by depletion of glutathione or by low external dosesof H₂O₂. Cycloheximide prevents apoptotic death revealing activeparticipation of the cell. Yeast can also be triggered intoapoptosis by a mutation in CDC48 or by expression of mammalianbax. In both cases, we show oxygen radicals to accumulate inthe cell, whereas radical depletion or hypoxia prevents apoptosis.These results suggest that the generation of oxygen radicalsis a key event in the ancestral apoptotic pathway and offer an explanation for the mechanism of bax-induced apoptosis inthe absence of any established apoptotic gene in yeast.

Key Words: apoptosis • glutathione • oxygen stress • reactive oxygen species • Saccharomyces cerevisiae

Abbreviations used in this paper: PBN, N-tert-butyl- ${alpha}$ –phenylnitrone; ROS, reactive oxygen species; SC, synthetic complete medium; TMPO, 3,3,5,5,-tetramethyl-pyrroline N-oxide; TUNEL, TdT-mediated dUTP nick end labeling.

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