Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast.
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.
Pozniakovsky
Andrei I
AI
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Knorre
Dmitry A
DA
Markova
Olga V
OV
Hyman
Anthony A
AA
Skulachev
Vladimir P
VP
Severin
Fedor F
FF
D000638:Amiodarone / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D007700:Kinetics; D000072235:Mating Factor; D008564:Membrane Potentials / Q000187:drug effects; D008689:Methacrylates; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010675:Pheromones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology
D000935:Antifungal Agents; D008689:Methacrylates; D024101:Mitochondrial Proteins; D010455:Peptides; D010675:Pheromones; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D013844:Thiazoles; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000072235:Mating Factor; D000968:Antimycin A; C030517:myxothiazol; D045304:Cytochromes c; D000638:Amiodarone; D010100:Oxygen; D002118:Calcium