Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders, Royal College of Surgeons in Ireland Dublin, Ireland.
Front Cell Neurosci. 2014 Sep 30;8:281. doi: 10.3389/fncel.2014.00281. eCollection 2014.
Cells under stress activate cell survival and cell death signaling pathways. Cell death signaling frequently converges on mitochondria, a process that is controlled by the activities of pro- and anti-apoptotic B-cell lymphoma 2 (BCL-2) proteins. In this review, we summarize current knowledge on the control of neuronal survival, development and injury by anti-apoptotic BCL-2 family proteins. We discuss overlapping and differential effects of the individual family members BCL-2, BCL-extra long (BCL-XL), myeloid cell leukemia 1 (MCL-1), and BCL2-like 2 (BCL-W) in the control of survival during development and pathophysiological processes such as trophic factor withdrawal, ischemic injury, excitotoxicity, oxidative stress and energy stress. Finally we discuss recent evidence that several anti-apoptotic BCL-2 proteins influence mitochondrial bioenergetics and control neuronal Ca(2+) homeostasis independent of their classical role in cell death signaling.
细胞在应激下会激活细胞存活和细胞死亡信号通路。细胞死亡信号经常汇聚到线粒体，这个过程受到促凋亡和抗凋亡 B 细胞淋巴瘤 2（BCL-2）蛋白活性的控制。在这篇综述中，我们总结了抗凋亡 BCL-2 家族蛋白对神经元存活、发育和损伤的控制的现有知识。我们讨论了个体家族成员 BCL-2、BCL-extra long（BCL-XL）、髓样细胞白血病 1（MCL-1）和 BCL2 样 2（BCL-W）在发育过程中以及营养因子撤离、缺血性损伤、兴奋毒性、氧化应激和能量应激等病理生理过程中对生存的控制的重叠和差异影响。最后，我们讨论了最近的证据，即几种抗凋亡 BCL-2 蛋白影响线粒体生物能学，并控制神经元 Ca（2+）稳态，而不依赖于它们在细胞死亡信号中的经典作用。
