Medical Research Council Mitochondrial Biology Unit, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0XY, UK.
Université de Lyon, Centre de Recherche en Cancérologie de Lyon, U1052 INSERM, UMR CNRS 5286, Université Lyon I, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France.
Int J Mol Sci. 2021 Apr 2;22(7):3730. doi: 10.3390/ijms22073730.
Bcl-2 family proteins are considered as one of the major regulators of apoptosis. Indeed, this family is known to control the mitochondrial outer membrane permeabilization (MOMP): a central step in the mitochondrial pathway of apoptosis. However, in recent years Bcl-2 family members began to emerge as a new class of intracellular calcium (Ca) regulators. At mitochondria-ER contacts (MERCs) these proteins are able to interact with major Ca transporters, thus controlling mitochondrial Ca homeostasis and downstream Ca signalling pathways. Beyond the regulation of cell survival, this Bcl-2-dependent control over the mitochondrial Ca dynamics has far-reaching consequences on the physiology of the cell. Here, we review how the Bcl-2 family of proteins mechanistically regulate mitochondrial Ca homeostasis and how this regulation orchestrates cell death/survival decisions as well as the non-apoptotic process of cell migration.
Bcl-2 家族蛋白被认为是细胞凋亡的主要调控因子之一。事实上，该家族已知能够控制线粒体膜通透性（MOMP）：这是细胞凋亡的线粒体途径中的一个关键步骤。然而，近年来 Bcl-2 家族成员开始成为细胞内钙（Ca）调节的新一类。在线粒体-内质网接触（MERCs）处，这些蛋白能够与主要的 Ca 转运蛋白相互作用，从而控制线粒体 Ca 稳态和下游 Ca 信号通路。除了对细胞存活的调节外，Bcl-2 依赖性对线粒体 Ca 动力学的控制对细胞的生理学有深远的影响。在这里，我们综述了 Bcl-2 家族蛋白如何通过机制调节线粒体 Ca 稳态，以及这种调节如何协调细胞死亡/存活决策以及非凋亡的细胞迁移过程。
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