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

2005; Rockefeller University Press; Volume: 168; Issue: 2 Linguagem: Inglês

10.1083/jcb.200408145

1540-8140

Andrei Pozniakovsky, Dmitry A. Knorre, О. В. Маркова, Anthony A. Hyman, Vladimir P. Skulachev, Fedor F. Severin,

Ion channel regulation and function

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.