One protein, different cell fate: the differential outcome of depleting GRP75 during oxidative stress in neurons.
One protein, different cell fate: the differential outcome of depleting GRP75 during oxidative stress in neurons.
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DOI：
10.1038/s41419-017-0148-7
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发表时间：
2018-01-18
影响因子：
9
通讯作者：
Dolga AM
中科院分区：
文献类型：
--
作者：
Honrath B;Culmsee C;Dolga AM
内质网（ER）和线粒体之间的相互连接，将Ca 2+转移到线粒体基质中，构成了细胞内Ca 2+信号传导的主要部分。通过增加线粒体Ca 2 +（[Ca 2 +] m）摄取，ER-线粒体串扰通过加速线粒体呼吸来增强能量产生，从而支持细胞功能和存活。电压依赖性阴离子通道1（VDAC 1）和热休克蛋白葡萄糖调节蛋白75（GRP 75）1。虽然IP 3R和VDAC 1是驱动Ca 2+通量的Ca 2+渗透性离子通道，但GRP 75对于维持细胞器之间的物理接触至关重要，从而促进Ca 2+信号传播到线粒体2中。来自骨、乳腺或结肠的肿瘤细胞中GRP 75表达降低与细胞死亡易感性增加有关，小分子GRP 75抑制药物被用作潜在的治疗干预3。然而，神经元或脑源性肿瘤细胞中GRP 75与ER-线粒体串扰的相关性在很大程度上是未知的。在生理条件下，GRP 75抑制似乎激活线粒体应激反应，例如人神经母细胞瘤SH-SY 5 Y细胞中的线粒体未折叠蛋白反应或自噬4。相反，在病理条件下，GRP 75表达发挥不同的作用。例如，在SH-SY 5 Y细胞中，
The interconnection between the endoplasmic reticulum (ER) and mitochondria to transfer Ca2+ into the mitochondrial matrix constitutes a major part of intracellular Ca2+ signaling. By increasing mitochondrial Ca2+([Ca2+] m) uptake, ER-mitochondrial crosstalk enhances energy production through accelerating mitochondrial respiration, thereby supporting cellular function and survival.ER-mitochondrial associations are established by multiprotein complexes formed, for instance, by ER-bound inositol-1, 4, 5-trisphosphate receptor (IP3R), mitochondriaresident voltage-dependent anion channel 1 (VDAC1) and the heat shock protein glucose-regulated protein 75 (GRP75) 1. While IP3R and VDAC1 are Ca2+-permeable ion channels driving Ca2+ flux, GRP75 is essential to maintain the physical contact between the organelles, thereby facilitating the propagation of the Ca2+ signal into the mitochondria 2. Reduced GRP75 expression in tumor cells derived from bone, breast or colon has been linked to an increased susceptibility to cell death, and small molecule GRP75-inhibitory drugs are exploited as a potential therapeutic intervention 3. However, the relevance of GRP75 for ER-mitochondrial crosstalk in neurons or brain-derived tumor cells is largely unknown. Under physiological conditions, GRP75 inhibition seemed to activate mitochondrial stress responses such as the mitochondrial unfolded protein response or autophagy in human neuroblastoma SH-SY5Y cells 4. In contrast, under pathological conditions, GRP75 expression exerted different effects. For instance, in SH-SY5Y cells
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影响因子：
9
作者：
通讯作者：
--
影响因子：
3.4
作者：
Guo, Weiwei;Yang, Ling;Zuo, Ji
通讯作者：
Zuo, Ji
影响因子：
7
作者：
Honrath B;Metz I;Bendridi N;Rieusset J;Culmsee C;Dolga AM
通讯作者：
Dolga AM
DOI：
10.1038/nrm.2015.8
发表时间：
2016-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8.1
作者：
Egnatchik RA;Leamy AK;Jacobson DA;Shiota M;Young JD
通讯作者：
Young JD