Mitochondrial Calcium: Effects of Its Imbalance in Disease.
Mitochondrial Calcium: Effects of Its Imbalance in Disease.
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DOI：
10.3390/antiox11050801
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发表时间：
2022-04-20
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影响因子：
--
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中科院分区：
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钙用于许多细胞过程，并以低浓度（约100 nM）的游离钙形式维持在细胞内（与细胞外（毫摩尔）浓度相比），以避免磷酸盐沉淀等不良影响。出于这个原因，细胞已经通过将钙区室化到线粒体和内质网（ER）中来适应缓冲策略。在线粒体中，钙浓度在毫摩尔范围内，就像它在ER中一样。线粒体积极地有助于缓冲细胞钙，但是如果基质钙增加超过生理需求，则其可以促进线粒体渗透性转换孔（mPTP）的打开，并且因此触发凋亡或坏死性细胞死亡。已经报道了mPTP开放在缺血-再灌注、肝脏、肌肉和溶酶体储存疾病以及影响中枢神经系统的疾病（例如帕金森病（PD）、阿尔茨海默病（AD）、亨廷顿病（HD）和肌萎缩性侧索硬化症（ALS））中的病理生理学意义。在这篇综述中，我们提出了一个更新的概述线粒体钙调节的主要细胞机制。我们特别关注与钙稳态失衡相关的神经退行性疾病，并总结了一些用于减轻这些疾病的治疗方法。
Calcium is used in many cellular processes and is maintained within the cell as free calcium at low concentrations (approximately 100 nM), compared with extracellular (millimolar) concentrations, to avoid adverse effects such as phosphate precipitation. For this reason, cells have adapted buffering strategies by compartmentalizing calcium into mitochondria and the endoplasmic reticulum (ER). In mitochondria, the calcium concentration is in the millimolar range, as it is in the ER. Mitochondria actively contribute to buffering cellular calcium, but if matrix calcium increases beyond physiological demands, it can promote the opening of the mitochondrial permeability transition pore (mPTP) and, consequently, trigger apoptotic or necrotic cell death. The pathophysiological implications of mPTP opening in ischemia-reperfusion, liver, muscle, and lysosomal storage diseases, as well as those affecting the central nervous system, for example, Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) have been reported. In this review, we present an updated overview of the main cellular mechanisms of mitochondrial calcium regulation. We specially focus on neurodegenerative diseases related to imbalances in calcium homeostasis and summarize some proposed therapies studied to attenuate these diseases.
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影响因子：
4
作者：
Austin S;Tavakoli M;Pfeiffer C;Seifert J;Mattarei A;De Stefani D;Zoratti M;Nowikovsky K
通讯作者：
Nowikovsky K
影响因子：
11.4
作者：
Area-Gomez, Estela;Castillo, Maria Del Carmen Lara;Tambini, Marc D.;Guardia-Laguarta, Cristina;de Groof, Ad J. C.;Madra, Moneek;Ikenouchi, Junichi;Umeda, Masato;Bird, Thomas D.;Sturley, Stephen L.;Schon, Eric A.
通讯作者：
Schon, Eric A.
影响因子：
5.1
作者：
Abdelkader, Noha F.;Safar, Marwa M.;Salem, Hesham A.
通讯作者：
Salem, Hesham A.
影响因子：
16.2
作者：
Agarwal A;Wu PH;Hughes EG;Fukaya M;Tischfield MA;Langseth AJ;Wirtz D;Bergles DE
通讯作者：
Bergles DE
影响因子：
64.8
作者：
Baughman, Joshua M.;Perocchi, Fabiana;Girgis, Hany S.;Plovanich, Molly;Belcher-Timme, Casey A.;Sancak, Yasemin;Bao, X. Robert;Strittmatter, Laura;Goldberger, Olga;Bogorad, Roman L.;Koteliansky, Victor;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.