Kaufman Randal J, Malhotra Jyoti D
Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Proteostasis Therapeutics, Cambridge, MA, USA.
Biochim Biophys Acta. 2014 Oct;1843(10):2233-9. doi: 10.1016/j.bbamcr.2014.03.022. Epub 2014 Mar 30.
Calcium homeostasis is central to all cellular functions and has been studied for decades. Calcium acts as a critical second messenger for both extracellular and intracellular signaling and is fundamental in cell life and death decisions (Berridge et al., 2000) [1]. The calcium gradient in the cell is coupled with an inherent ability of the divalent cation to reversibly bind multiple target biological molecules to generate an extremely versatile signaling system [2]. Calcium signals are used by the cell to control diverse processes such as development, neurotransmitter release, muscle contraction, metabolism, autophagy and cell death. "Cellular calcium overload" is detrimental to cellular health, resulting in massive activation of proteases and phospholipases leading to cell death (Pinton et al., 2008) [3]. Historically, cell death associated with calcium ion perturbations has been primarily recognized as necrosis. Recent evidence clearly associates changes in calcium ion concentrations with more sophisticated forms of cellular demise, including apoptosis (Kruman et al., 1998; Tombal et al., 1999; Lynch et al., 2000; Orrenius et al., 2003) [4-7]. Although the endoplasmic reticulum (ER) serves as the primary calcium store in the metazoan cell, dynamic calcium release to the cytosol, mitochondria, nuclei and other organelles orchestrate diverse coordinated responses. Most evidence supports that calcium transport from the ER to mitochondria plays a significant role in regulating cellular bioenergetics, production of reactive oxygen species, induction of autophagy and apoptosis. Recently, molecular identities that mediate calcium traffic between the ER and mitochondria have been discovered (Mallilankaraman et al., 2012a; Mallilankaraman et al., 2012b; Sancak et al., 2013)[8-10]. The next questions are how they are regulated for exquisite tight control of ER-mitochondrial calcium dynamics. This review attempts to summarize recent advances in the role of calcium in regulation of ER and mitochondrial function. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.
钙稳态是所有细胞功能的核心，并且已经被研究了数十年。钙作为细胞外和细胞内信号传导的关键第二信使，在细胞生死抉择中起着至关重要的作用（Berridge等人，2000年）[1]。细胞内的钙梯度与二价阳离子可逆结合多个靶生物分子以产生极其通用的信号系统的固有能力相关联[2]。细胞利用钙信号来控制各种过程，如发育、神经递质释放、肌肉收缩、代谢、自噬和细胞死亡。“细胞钙超载”对细胞健康有害，会导致蛋白酶和磷脂酶大量激活，从而导致细胞死亡（Pinton等人，2008年）[3]。从历史上看，与钙离子扰动相关的细胞死亡主要被认为是坏死。最近的证据清楚地表明，钙离子浓度的变化与更复杂的细胞死亡形式有关，包括凋亡（Kruman等人，1998年；Tombal等人，1999年；Lynch等人，2000年；Orrenius等人，2003年）[4 - 7]。尽管内质网（ER）是后生动物细胞中的主要钙库，但向细胞质、线粒体、细胞核和其他细胞器的动态钙释放协调了各种不同的反应。大多数证据支持从内质网到线粒体的钙转运在调节细胞生物能学、活性氧的产生、自噬和凋亡的诱导中起重要作用。最近，已经发现了介导内质网和线粒体之间钙运输的分子身份（Mallilankaraman等人，2012年a；Mallilankaraman等人，2012年b；Sancak等人，2013年）[8 - 10]。接下来的问题是它们如何被调节以精确严格地控制内质网 - 线粒体钙动力学。本综述试图总结钙在调节内质网和线粒体功能方面作用的最新进展。本文是名为：健康与疾病中的钙信号传导的特刊的一部分。客座编辑：Geert Bultynck、Jacques Haiech、Claus W. Heizmann、Joachim Krebs和Marc Moreau。
