Bonneau Benjamin, Prudent Julien, Popgeorgiev Nikolay, Gillet Germain
Université de Lyon, Lyon, France.
Biochim Biophys Acta. 2013 Jul;1833(7):1755-65. doi: 10.1016/j.bbamcr.2013.01.021. Epub 2013 Jan 27.
The existence of the bcl-2 (B-cell lymphoma-2) gene was reported nearly 30 years ago. Yet, Bcl-2 family group of proteins still surprises us with their structural and functional diversity. Since the discovery of the Bcl-2 family of proteins as one of the main apoptosis judges, the precise mechanism of their action remains a hot topic of intensive scientific research and debates. Although extensive work has been performed on the role of mitochondria in apoptosis, more and more studies point out an implication of the endoplasmic reticulum in this process. Interestingly, Bcl-2 family proteins could be localized to both the mitochondria and the endoplasmic reticulum highlighting their crucial role in apoptosis control. In particular, in these organelles Bcl-2 proteins seem to be involved in calcium homeostasis regulation although the mechanisms underlying this function are still misunderstood. We now assume with high degree of certainty that the majority of Bcl-2 family members take part not only in apoptosis regulation but also in other processes important for the cell physiology briefly denominated as "non-apoptotic" functions. Drawing a complete and comprehensive image of Bcl-2 family requires the understanding of their implications in all cellular processes. Here, we review the current knowledge on the control of calcium homeostasis by the Bcl-2 family at the endoplasmic reticulum and at the mitochondria. Then we focus on the non-apoptotic functions of the Bcl-2 proteins in relation with the regulation of this versatile intracellular messenger. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
bcl - 2（B细胞淋巴瘤 - 2）基因的存在早在近30年前就有报道。然而，Bcl - 2蛋白家族在结构和功能上的多样性仍然让我们感到惊讶。自从发现Bcl - 2蛋白家族是细胞凋亡的主要调控因子之一以来，其确切的作用机制仍然是科学研究和争论的热点话题。尽管已经对线粒体在细胞凋亡中的作用进行了大量研究，但越来越多的研究指出内质网也参与了这一过程。有趣的是，Bcl - 2家族蛋白可定位于线粒体和内质网，这突出了它们在细胞凋亡控制中的关键作用。特别是，在这些细胞器中，Bcl - 2蛋白似乎参与了钙稳态的调节，尽管其潜在机制仍不清楚。我们现在高度确定地认为，大多数Bcl - 2家族成员不仅参与细胞凋亡的调控，还参与其他对细胞生理重要的过程，简称为“非凋亡”功能。要全面了解Bcl - 2家族，需要了解它们在所有细胞过程中的作用。在这里，我们综述了目前关于Bcl - 2家族在内质网和线粒体中对钙稳态调控的认识。然后我们将重点关注Bcl - 2蛋白与这种多功能细胞内信使调节相关的非凋亡功能。本文是名为“第12届欧洲钙研讨会”的特刊的一部分。
