Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.
Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.
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DOI：
10.1083/jcb.200108103
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发表时间：
2002-06-24
期刊：
影响因子：
--
通讯作者：
Ogawa S
中科院分区：
文献类型：
--
作者：
Hori O;Ichinoda F;Tamatani T;Yamaguchi A;Sato N;Ozawa K;Kitao Y;Miyazaki M;Harding HP;Ron D;Tohyama M;M Stern D;Ogawa S
线粒体ATP依赖性蛋白酶Lon的大鼠同源物从暴露于缺氧的培养星形胶质细胞中克隆。Lon的表达在体外由缺氧或ER应激增强，在体内由脑缺血增强。这些观察结果表明，由ER应激引发的核基因表达（Lon）的变化有可能影响重要的线粒体过程，如细胞色素c氧化酶（考克斯）的组装和/或降解。事实上，稳态水平的核编码的考克斯IV和V的减少，并迅速降解的ER应激下的MAL编码的亚基II。放线菌酮处理的细胞引起了类似的不平衡的积累考克斯亚基，并增强mRNA的Lon和Yme 1，后者的另一个线粒体ATP依赖性蛋白酶。此外，在PERK（-/-）细胞中，ER应激对Lon或GRP 75/mtHSP 70的诱导受到抑制。转染研究表明，野生型或蛋白水解活性Lon的过度表达促进考克斯II组装成一个考克斯I-含有复杂的，并部分防止由布雷菲德菌素A或缺氧引起的线粒体功能障碍。这些观察结果表明，由于ER应激导致的蛋白质合成的抑制对垂体相关蛋白的合成具有复杂的影响，所述垂体相关蛋白包括考克斯亚基和ATP依赖性蛋白酶和/或分子伴侣，所述蛋白酶和/或分子伴侣有助于考克斯复合物的组装。
The rat homologue of a mitochondrial ATP-dependent protease Lon was cloned from cultured astrocytes exposed to hypoxia. Expression of Lon was enhanced in vitro by hypoxia or ER stress, and in vivo by brain ischemia. These observations suggested that changes in nuclear gene expression (Lon) triggered by ER stress had the potential to impact important mitochondrial processes such as assembly and/or degradation of cytochrome c oxidase (COX). In fact, steady-state levels of nuclear-encoded COX IV and V were reduced, and mitochondrial-encoded subunit II was rapidly degraded under ER stress. Treatment of cells with cycloheximide caused a similar imbalance in the accumulation of COX subunits, and enhanced mRNA for Lon and Yme1, the latter another mitochondrial ATP-dependent protease. Furthermore, induction of Lon or GRP75/mtHSP70 by ER stress was inhibited in PERK (−/−) cells. Transfection studies revealed that overexpression of wild-type or proteolytically inactive Lon promoted assembly of COX II into a COX I–containing complex, and partially prevented mitochondrial dysfunction caused by brefeldin A or hypoxia. These observations demonstrated that suppression of protein synthesis due to ER stress has a complex effect on the synthesis of mitochondrial-associated proteins, both COX subunits and ATP-dependent proteases and/or chaperones contributing to assembly of the COX complex.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
16
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作者：
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