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酵母细胞的凋亡:触发因素、途径、子程序。

Apoptosis in yeast: triggers, pathways, subroutines.

机构信息

Institute of Molecular Biosciences, Karl-Franzens University, Graz, Austria.

出版信息

Cell Death Differ. 2010 May;17(5):763-73. doi: 10.1038/cdd.2009.219. Epub 2010 Jan 15.

Abstract

A cell's decision to die is controlled by a sophisticated network whose deregulation contributes to the pathogenesis of multiple diseases including neoplastic and neurodegenerative disorders. The finding, more than a decade ago, that baker's yeast (Saccharomyces cerevisiae) can undergo apoptosis uncovered the possibility to investigate this mode of programmed cell death (PCD) in a model organism that combines both technical advantages and a eukaryotic 'cell room.' Since then, numerous exogenous and endogenous triggers have been found to induce yeast apoptosis and multiple yeast orthologs of crucial metazoan apoptotic regulators have been identified and characterized at the molecular level. Such apoptosis-relevant orthologs include proteases such as the yeast caspase as well as several mitochondrial and nuclear proteins that contribute to the execution of apoptosis in a caspase-independent manner. Additionally, physiological scenarios such as aging and failed mating have been discovered to trigger apoptosis in yeast, providing a teleological interpretation of PCD affecting a unicellular organism. Due to its methodological and logistic simplicity, yeast constitutes an ideal model organism that is efficiently helping to decipher the cell death regulatory network of higher organisms, including the switches between apoptotic, autophagic, and necrotic pathways of cellular catabolism. Here, we provide an overview of the current knowledge about the apoptotic subroutine of yeast PCD and its regulation.

摘要

细胞的死亡决定是由一个复杂的网络控制的,其失调导致了多种疾病的发病机制,包括肿瘤和神经退行性疾病。十多年前,人们发现面包酵母(酿酒酵母)可以发生细胞凋亡,这就为在一种兼具技术优势和真核“细胞室”的模式生物中研究这种程序性细胞死亡(PCD)提供了可能。自那时以来,已经发现了许多外源性和内源性触发因素来诱导酵母细胞凋亡,并且已经在分子水平上鉴定和表征了多种酵母中与关键多细胞动物凋亡调节剂同源的蛋白。与凋亡相关的同源蛋白包括酵母半胱天冬酶等蛋白酶,以及几种线粒体和核蛋白,它们以不依赖半胱天冬酶的方式参与凋亡的执行。此外,还发现衰老和交配失败等生理情况会引发酵母细胞凋亡,为影响单细胞生物的 PCD 提供了一种目的论解释。由于其方法学和逻辑上的简单性,酵母成为了一种理想的模式生物,它正在有效地帮助我们破译高等生物的细胞死亡调控网络,包括细胞分解代谢中凋亡、自噬和坏死途径之间的转换。在这里,我们概述了目前关于酵母 PCD 的凋亡子程序及其调控的知识。

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