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Published 18 January 2005. doi:10.1083/jcb.200408145
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 2, 257-269
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Article

Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast



Andrei I. Pozniakovsky1, Dmitry A. Knorre2, Olga V. Markova2, Anthony A. Hyman1, Vladimir P. Skulachev2, and Fedor F. Severin3

1 Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
2 A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia
3 BioTechnological Center, Proteomics and Cellular Machines, University of Technology Dresden, D-01307 Dresden, Germany

Correspondence to Fedor F. Severin: severin{at}mpi-cdg.de

Although programmed cell death (PCD) is extensively studied in multicellular organisms, in recent years it has been shown that a unicellular organism, yeast Saccharomyces cerevisiae, also possesses death program(s). In particular, we have found that a high doses of yeast pheromone is a natural stimulus inducing PCD. Here, we show that the death cascades triggered by pheromone and by a drug amiodarone are very similar. We focused on the role of mitochondria during the pheromone/amiodarone-induced PCD. For the first time, a functional chain of the mitochondria-related events required for a particular case of yeast PCD has been revealed: an enhancement of mitochondrial respiration and of its energy coupling, a strong increase of mitochondrial membrane potential, both events triggered by the rise of cytoplasmic [Ca2+], a burst in generation of reactive oxygen species in center o of the respiratory chain complex III, mitochondrial thread-grain transition, and cytochrome c release from mitochondria. A novel mitochondrial protein required for thread-grain transition is identified.

A.I. Pozniakovsky, D.A. Knorre, and O.V. Markova contributed equally to this paper.

Abbreviations used in this paper: {Delta}{Psi}, mitochondrial transmembrane electric potential difference; FCCP, trifluoromethoxycarbonylcyanide phenylhydrazone; H2DCF-DA, dichlorofluorescin diacetate; NAC, N-acetyl cysteine; PCD, programmed cell death; ROS, reactive oxygen species.


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