Role of Mitochondria in the Pheromone- And Amiodarone-Induced Programmed Death of Yeast

J Cell Biol. 2005 Jan 17;168(2):257-69. doi: 10.1083/jcb.200408145.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiodarone / pharmacology*
  • Antifungal Agents / pharmacology
  • Antimycin A / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Calcium / metabolism
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cytochromes c / metabolism
  • DNA Fragmentation / drug effects
  • Kinetics
  • Mating Factor
  • Membrane Potentials / drug effects
  • Methacrylates
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / physiology*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology
  • Models, Biological
  • Oxygen / metabolism
  • Peptides / pharmacology
  • Pheromones / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Thiazoles / pharmacology

Substances

  • Antifungal Agents
  • Methacrylates
  • Mitochondrial Proteins
  • Peptides
  • Pheromones
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • Thiazoles
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • Mating Factor
  • Antimycin A
  • myxothiazol
  • Cytochromes c
  • Amiodarone
  • Oxygen
  • Calcium