Institut de Biochimie et de Génétique Cellulaires, Université de Bordeaux, CNRS, UMR 5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.
Int J Mol Sci. 2021 Apr 15;22(8):4086. doi: 10.3390/ijms22084086.
BCL-2 family members are major regulators of apoptotic cell death in mammals. They form an intricate regulatory network that ultimately regulates the release of apoptogenic factors from mitochondria to the cytosol. The ectopic expression of mammalian BCL-2 family members in the yeast which lacks BCL-2 homologs, has been long established as a useful addition to the available models to study their function and regulation. In yeast, individual proteins can be studied independently from the whole interaction network, thus providing insight into the molecular mechanisms underlying their function in a living context. Furthermore, one can take advantage of the powerful tools available in yeast to probe intracellular trafficking processes such as mitochondrial sorting and interactions/exchanges between mitochondria and other compartments, such as the endoplasmic reticulum that are largely conserved between yeast and mammals. Yeast molecular genetics thus allows the investigation of the role of these processes on the dynamic equilibrium of BCL-2 family members between mitochondria and extramitochondrial compartments. Here we propose a model of dynamic regulation of BCL-2 family member localization, based on available evidence from ectopic expression in yeast.
BCL-2 家族成员是哺乳动物细胞凋亡的主要调节因子。它们形成一个复杂的调节网络，最终调节凋亡因子从线粒体向细胞质的释放。在缺乏 BCL-2 同源物的酵母中异位表达哺乳动物 BCL-2 家族成员，长期以来一直被认为是研究其功能和调节的有用模型的补充。在酵母中，可以独立于整个相互作用网络研究单个蛋白质，从而深入了解其在活细胞环境中的功能的分子机制。此外，人们可以利用酵母中提供的强大工具来研究细胞内运输过程，如线粒体的分拣以及线粒体与其他细胞器（如内质网）之间的相互作用/交换，这些过程在酵母和哺乳动物之间是高度保守的。因此，酵母分子遗传学允许研究这些过程对 BCL-2 家族成员在线粒体和细胞外细胞器之间的动态平衡的作用。在这里，我们提出了一个基于酵母异位表达的可用证据的 BCL-2 家族成员定位的动态调节模型。
