Glutathione and mitochondria.
Glutathione and mitochondria.
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DOI：
10.3389/fphar.2014.00151
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发表时间：
2014
影响因子：
5.6
通讯作者：
Fernández-Checa JC
中科院分区：
文献类型：
--
作者：
Ribas V;García-Ruiz C;Fernández-Checa JC
谷胱甘肽（GSH）是细胞中主要的非蛋白质硫醇，其功能依赖于其半胱氨酸部分的氧化还原活性硫醇，该半胱氨酸部分充当许多抗氧化剂和解毒酶的辅因子。虽然GSH仅在胞质溶胶中由其组成氨基酸合成，但其分布在不同的隔室中，包括线粒体，其中其在基质中的浓度等于胞质溶胶中的浓度。这一特点及其在生理pH值下的负电荷意味着存在特定的载体将GSH从细胞质导入线粒体基质，在那里它在防御呼吸诱导的活性氧以及脂质氢过氧化物和亲电子体的解毒中起着关键作用。此外，由于线粒体在细胞死亡的激活和模式中发挥核心战略作用，线粒体GSH已显示出关键性地调节对二次撞击的致敏水平，所述二次撞击诱导线粒体膜透化和限制在膜间空间中的蛋白质的释放，所述蛋白质一旦在胞质溶胶中就参与细胞死亡的分子机制。在这篇综述中，我们总结了最近的数据，线粒体谷胱甘肽的调节和细胞死亡和流行的人类疾病，如癌症，脂肪肝疾病，阿尔茨海默氏病的作用。
Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer’s disease.
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影响因子：
9.2
作者：
Bosch, Marta;Mari, Montserrat;Herms, Albert;Fernandez, Ana;Fajardo, Alba;Kassan, Adam;Giralt, Albert;Colell, Anna;Balgoma, David;Barbero, Elisabet;Gonzalez-Moreno, Elena;Matias, Nuria;Tebar, Francesc;Balsinde, Jesus;Camps, Marta;Enrich, Carlos;Gross, Steven P.;Garcia-Ruiz, Carmen;Perez-Navarro, Esther;Fernandez-Checa, Jose C.;Pol, Albert
通讯作者：
Pol, Albert
DOI：
10.1073/pnas.152168599
发表时间：
2002-07-23
影响因子：
11.1
作者：
Casagrande, S;Bonetto, V;Ghezzi, P
通讯作者：
Ghezzi, P
DOI：
10.1073/pnas.94.21.11540
发表时间：
1997-10-14
影响因子：
11.1
作者：
Caron, KM;Soo, SC;Parker, KL
通讯作者：
Parker, KL
影响因子：
4.8
作者：
Beer, SM;Taylor, ER;Murphy, MP
通讯作者：
Murphy, MP
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD