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

Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast.
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线粒体在信息素酮和胺碘酮诱导的酵母死亡中的作用。

DOI:
10.1083/jcb.200408145
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发表时间:
2005-01-17
影响因子:
7.8
通讯作者:
Severin, Fedor F
Severin, Fedor F
中科院分区:
生物学1区
文献类型:
--
作者:
Pozniakovsky, Andrei I;Knorre, Dmitry A;Markova, Olga V;Hyman, Anthony A;Skulachev, Vladimir P;Severin, Fedor F

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尽管细胞程序性死亡在多细胞生物中得到了广泛的研究,但近年来的研究表明,单细胞生物酿酒酵母也具有死亡程序(S)。特别是,我们发现高剂量的酵母信息素是一种诱发PCD的自然刺激。在这里,我们展示了信息素和药物胺碘酮引发的死亡级联非常相似。我们重点研究了线粒体在信息素/胺碘酮诱导的PCD中的作用。首次揭示了酵母PCD所需的线粒体相关事件的功能链:线粒体呼吸及其能量耦合的增强,线粒体膜电位的显著增加,这两种事件都是由细胞质[Ca~(2+)]的升高,呼吸链复合体III的中心O产生的活性氧的突然产生,线粒体的线粒过渡和细胞色素c的释放所引发的。鉴定了一种新的线粒过渡所需的线粒体蛋白。
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.