Regulation of Endoplasmic Reticulum-Mitochondria Ca(2+) Transfer and Its Importance for Anti-Cancer Therapies.
Regulation of Endoplasmic Reticulum-Mitochondria Ca(2+) Transfer and Its Importance for Anti-Cancer Therapies.
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DOI：
10.3389/fonc.2017.00180
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发表时间：
2017
影响因子：
4.7
通讯作者：
Pinton P
中科院分区：
文献类型：
--
作者：
Pedriali G;Rimessi A;Sbano L;Giorgi C;Wieckowski MR;Previati M;Pinton P
细胞器间膜接触部位是调节细胞内钙离子浓度和分布的主要部位。在这里，细胞外刺激在广泛的通道、泵和离子交换器上工作，以在几个隔室之间重新分配细胞内的钙离子。由此产生的钙离子运动的高度明确的空间和时间模式可以用来引发特定的细胞反应，包括细胞增殖、迁移或死亡。质膜(PM)还可以通过小凹直接与线粒体和内质网(ER)接触，小凹是质膜的小内陷，确保细胞器之间的接触，并通过小窝蛋白等支架蛋白参与多种细胞功能的调节。PM和ER组织专门的交汇点。在这里，受体依赖的钙信号的许多成分聚集在一起，包括ORAI1-间质相互作用分子1复合体。这种复合体构成了钙离子进入非兴奋性细胞的主要机制，受细胞内钙离子的调节。内质网和线粒体之间的几个接触部位，被称为线粒体相关膜，显示出非常复杂和专门化的结构，并拥有大量调节钙离子转运的蛋白质。在这篇综述中，我们总结了几个癌基因和肿瘤抑制因子在这些特殊检查点的特殊作用的最新知识，并分析了针对细胞器间接触的钙离子流动以改变癌细胞的代谢和命运的抗癌治疗。
Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca2+ concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca2+ among several compartments. The resulting highly defined spatial and temporal patterns of Ca2+ movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins. PM and ER organize specialized junctions. Here, many components of the receptor-dependent Ca2+ signals are clustered, including the ORAI1-stromal interaction molecule 1 complex. This complex constitutes a primary mechanism for Ca2+ entry into non-excitable cells, modulated by intracellular Ca2+. Several contact sites between the ER and mitochondria, termed mitochondria-associated membranes, show a very complex and specialized structure and host a wide number of proteins that regulate Ca2+ transfer. In this review, we summarize current knowledge of the particular action of several oncogenes and tumor suppressors at these specialized check points and analyze anti-cancer therapies that specifically target Ca2+ flow at the inter-organelle contacts to alter the metabolism and fate of the cancer cell.
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DOI：
10.1042/bj20111114
发表时间：
2012-05-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Dremina ES;Sharov VS;Schöneich C
通讯作者：
Schöneich C
影响因子：
16
作者：
Dong Z;Shanmughapriya S;Tomar D;Siddiqui N;Lynch S;Nemani N;Breves SL;Zhang X;Tripathi A;Palaniappan P;Riitano MF;Worth AM;Seelam A;Carvalho E;Subbiah R;Jaña F;Soboloff J;Peng Y;Cheung JY;Joseph SK;Caplan J;Rajan S;Stathopulos PB;Madesh M
通讯作者：
Madesh M
影响因子：
82.9
作者：
Ablain, Julien;Rice, Kim;de The, Hugues
通讯作者：
de The, Hugues
影响因子：
3.5
作者：
Engelman, JA;Zhang, XL;Lisanti, MP
通讯作者：
Lisanti, MP
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Bettigole SE;Glimcher LH
通讯作者：
Glimcher LH