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

• Published in: The Journal of cell biology 2005-01, Vol.168 (2), p.257-269
• Main Authors: Pozniakovsky, Andrei I, Knorre, Dmitry A, Markova, Olga V, Hyman, Anthony A, Skulachev, Vladimir P, Severin, Fedor F
• Format: Article
• Language: English
• Subjects: Amiodarone - pharmacology; Antifungal Agents - pharmacology; Antimycin A - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Calcium - metabolism; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology; Cell cycle; Cell death; Cells; Cellular biology; Cytochromes; Cytochromes c - metabolism; DNA Fragmentation - drug effects; Kinetics; Mating Factor; Membrane Potentials - drug effects; Methacrylates; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - physiology; Mitochondrial DNA; Mitochondrial membranes; Mitochondrial Proteins - genetics; Mitochondrial Proteins - physiology; Models, Biological; Oxygen - metabolism; Peptides - pharmacology; Pheromones; Pheromones - pharmacology; Reactive Oxygen Species - metabolism; Respiration; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - metabolism; T lymphocytes; Thiazoles - pharmacology; Yeast; Yeasts
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200408145

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.