The product of the UTH1 gene, required for Bax-induced cell death in yeast, is involved in the response to rapamycin
The product of the UTH1 gene, required for Bax-induced cell death in yeast, is involved in the response to rapamycin
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DOI：
10.1046/j.1365-2958.2003.03311.x
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发表时间：
2003-01-01
影响因子：
3.6
通讯作者：
Manon, S
中科院分区：
文献类型：
--
作者：
Camougrand, N;Grelaud-Coq, A;Manon, S
分离到一株能抵抗Bax诱导的细胞死亡的酵母突变体。它支持一种突变，导致蛋白质Uth1p的数量减少。UTH1基因被破坏的菌株也表现出对Bax表达的抗性。Uth1p的缺失不会改变Bax的线粒体定位、插入线粒体外膜或其细胞色素c释放活性。另一方面，Uth1p的缺失确实阻止了酵母中与Bax表达相关的其他标志的出现，如乙醇胁迫后线粒体脂质的氧化、活性氧的产生和质膜性质的维持。缺乏Uth1p还可以诱导对雷帕霉素的抗性，雷帕霉素是自噬的特异性诱导剂。这种抗性仅在细胞在呼吸条件下生长时出现，而在发酵条件下不出现，这表明Uth1p通过涉及线粒体的自噬途径发挥作用，这与其主要位于线粒体膜外的位置一致。综上所述，这些数据表明，Bax能够在酵母中激活与自噬相关的死亡途径，这也表现出典型的细胞凋亡特征，揭示了Bax在这两种死亡类型中可能的双重功能。这一假说是根据对哺乳动物细胞中的细胞凋亡和自噬的共同调节的观察结果来讨论的。
A yeast mutant was isolated that was resistant to Bax-induced cell death. It supports a mutation leading to decreased amounts of the protein Uth1p. A strain in which the UTH1 gene is disrupted also exhibits resistance to Bax expression. The absence of Uth1p does not change the mitochondrial localization of Bax, its insertion in the mitochondrial outer membrane or its cytochrome c-releasing activity. On the other hand, the absence of Uth1p does prevent the appearance of other hallmarks related to Bax expression in yeast, such as oxidation of mitochondrial lipid, production of reactive oxygen species and maintenance of plasma membrane properties after ethanol stress. The absence of Uth1p was also found to induce resistance to rapamycin, a specific inducer of autophagy. This resistance only appears when cells are grown under respiratory conditions, but not under fermentative conditions, suggesting that Uth1p acts in an autophagic pathway involving mitochondria, in accordance with its main localization in the outer mitochondrial membrane. Taken together, these data show that Bax is able to activate a death pathway related to autophagy in yeast, which also exhibits typical hallmarks of apoptosis, revealing a possible dual function of Bax in both types of death. This hypothesis is discussed in the light of observations suggesting a coregulation of apoptosis and autophagy in mammalian cells.