Dubois Charlotte, Prevarskaya Natalia, Vanden Abeele Fabien
Inserm U1003, Equipe labellisée par la Ligue Nationale Contre le Cancer, SIRIC ONCOLille, Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, 59650 France, Laboratory of Excellence, Ion Channels Science and Therapeutics, France.
Biochim Biophys Acta. 2016 Jun;1863(6 Pt B):1337-43. doi: 10.1016/j.bbamcr.2015.11.033. Epub 2015 Nov 30.
Here, we review the role of Ca(2+) in apoptosis, namely that ER Ca(2+) depletion or a sustained elevation of cytosolic or mitochondrial Ca(2+) concentration are sufficient to trigger apoptosis. These concepts have emerged by the use of ER stressor agents that decrease the ER Ca(2+) pool by inhibiting SERCA pumps. However, aside from their well-known actions on Ca(2+) homeostasis disruption leading to apoptosis, new evidence show that some ER Ca(2+) modulators have significant implications in other Ca(2+)-mediated or Ca(2+)-independent pathways determining cell fate suggesting a more complex regulation of apoptosis by intracellular Ca(2+). Here, we discuss the crucial interplay between Ca(2+) mediated apoptosis, the Unfold Protein Response and autophagy determining cell fate, and the molecular compounds that have been used to depict these pathways. This review of the literature clearly shows the need for new inhibitors that do not interfere concomitantly with autophagy and Ca(2+) signaling. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.
在此，我们综述了钙离子（Ca(2+)）在细胞凋亡中的作用，即内质网（ER）钙离子耗竭或胞质或线粒体钙离子浓度持续升高足以触发细胞凋亡。这些概念是通过使用内质网应激剂得出的，这些应激剂通过抑制肌浆网Ca(2+) - ATP酶（SERCA）泵来减少内质网钙离子池。然而，除了它们对钙离子稳态破坏导致细胞凋亡的众所周知的作用外，新证据表明一些内质网钙离子调节剂在其他由钙离子介导或不依赖钙离子的决定细胞命运的途径中具有重要意义，这表明细胞内钙离子对细胞凋亡的调控更为复杂。在此，我们讨论了钙离子介导的细胞凋亡、未折叠蛋白反应和自噬之间决定细胞命运的关键相互作用，以及用于描述这些途径的分子化合物。对文献的综述清楚地表明，需要新的抑制剂，这些抑制剂不会同时干扰自噬和钙离子信号传导。本文是名为“钙与细胞命运”特刊的一部分。客座编辑：雅克·海耶克、克劳斯·海兹曼、约阿希姆·克雷布斯、蒂埃里·卡皮奥德和奥利维耶·米涅。
