Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská Dolina CH1, Ilkovičova 6, 84215 Bratislava, Slovakia.
Int J Mol Sci. 2023 Jul 27;24(15):12011. doi: 10.3390/ijms241512011.
Permeabilization of mitochondrial membrane by proteins of the BCL-2 family is a key decisive event in the induction of apoptosis in mammalian cells. Although yeast does not have homologs of the BCL-2 family, when these are expressed in yeast, they modulate the survival of cells in a way that corresponds to their activity in mammalian cells. The yeast gene, alternatively referred to as or , encodes for membrane protein in the endoplasmic reticulum that was, contradictorily, shown to either inhibit Bax or to be required for Bax activity. We have tested the effect of the deletion of this gene on the pro-apoptotic activity of Bax and Bak and the anti-apoptotic activity of Bcl-XL and Bcl-2, as well on survival after treatment with inducers of regulated cell death in yeast, hydrogen peroxide and acetic acid. While deletion resulted in increased sensitivity to acetic acid, it did not affect the sensitivity to hydrogen peroxide nor to BCL-2 family members. Thus, our results do not support any model in which the activity of BCL-2 family members is directly affected by but rather indicate that it may participate in modulating survival in response to some specific forms of stress.
BCL-2 家族蛋白对线粒体膜的通透化是诱导哺乳动物细胞凋亡的关键决定事件。尽管酵母没有 BCL-2 家族的同源物，但当这些蛋白在酵母中表达时，它们会以与在哺乳动物细胞中相似的方式调节细胞的存活。酵母基因，也被称为 或 ，编码内质网膜蛋白，该蛋白具有矛盾的作用，既可以抑制 Bax，也可以激活 Bax 的活性。我们已经测试了该基因缺失对 Bax 和 Bak 的促凋亡活性以及 Bcl-XL 和 Bcl-2 的抗凋亡活性的影响，以及酵母中受调控细胞死亡诱导剂（过氧化氢和乙酸）处理后的存活情况。虽然缺失导致对乙酸的敏感性增加，但对过氧化氢或 BCL-2 家族成员的敏感性没有影响。因此，我们的结果不支持 BCL-2 家族成员的活性直接受 影响的任何模型，而是表明它可能参与调节对某些特定形式应激的存活。
