Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amiodarone / pharmacology*
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Antifungal Agents / pharmacology
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Antimycin A / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Calcium / metabolism
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
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Cytochromes c / metabolism
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DNA Fragmentation / drug effects
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Kinetics
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Mating Factor
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Membrane Potentials / drug effects
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Methacrylates
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / physiology*
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / physiology
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Models, Biological
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Oxygen / metabolism
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Peptides / pharmacology
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Pheromones / pharmacology*
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Reactive Oxygen Species / metabolism
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae / physiology*
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Saccharomyces cerevisiae Proteins / metabolism
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Thiazoles / pharmacology
Substances
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Antifungal Agents
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Methacrylates
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Mitochondrial Proteins
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Peptides
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Pheromones
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Reactive Oxygen Species
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Saccharomyces cerevisiae Proteins
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Thiazoles
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
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Mating Factor
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Antimycin A
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myxothiazol
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Cytochromes c
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Amiodarone
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Oxygen
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Calcium