CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.
LaBCT, ICO, Saint Herblain, France.
Cell Death Dis. 2021 Feb 15;12(2):182. doi: 10.1038/s41419-021-03471-8.
In this work, we have explored the subcellular localization of Bcl2, a major antiapoptotic protein. In U251 glioma cells, we found that Bcl2 is localized mainly in the ER and is translocated to MAM and mitochondria upon induction of apoptosis; this mitochondrial transfer was not restricted to the demonstrator cell line, even if cell-specific modulations exist. We found that the Bcl2/mitochondria interaction is controlled by TOM20, a protein that belongs to the protein import machinery of the mitochondrial outer membrane. The expression of a small domain of interaction of TOM20 with Bcl2 potentiates its anti-apoptotic properties, which suggests that the Bcl2-TOM20 interaction is proapoptotic. The role of MAM and TOM20 in Bcl2 apoptotic mitochondrial localization and function has been confirmed in a yeast model in which the ER-mitochondria encounter structure (ERMES) complex (required for MAM stability in yeast) has been disrupted. Bcl2-TOM20 interaction is thus an additional player in the control of apoptosis.
在这项工作中，我们探讨了 Bcl2 的亚细胞定位，Bcl2 是一种主要的抗凋亡蛋白。在 U251 神经胶质瘤细胞中，我们发现 Bcl2 主要定位于内质网 (ER)，并在诱导细胞凋亡时易位到 MAM 和线粒体;这种线粒体转移不仅限于演示细胞系，即使存在细胞特异性的调节。我们发现 Bcl2/线粒体相互作用受 TOM20 控制，TOM20 是一种属于线粒体外膜蛋白输入机制的蛋白质。与 Bcl2 相互作用的 TOM20 的小结构域的表达增强了其抗凋亡特性，这表明 Bcl2-TOM20 相互作用是促凋亡的。在酵母模型中已经证实了 MAM 和 TOM20 在 Bcl2 凋亡性线粒体定位和功能中的作用，该模型中断了 ER-线粒体接触结构 (ERMES) 复合物 (酵母中 MAM 稳定性所必需的)。因此，Bcl2-TOM20 相互作用是凋亡控制的另一个参与者。
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