TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression.
TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression.
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DOI：
10.1371/journal.pone.0051912
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Katayama T
中科院分区：
文献类型：
--
作者：
Takamura H;Koyama Y;Matsuzaki S;Yamada K;Hattori T;Miyata S;Takemoto K;Tohyama M;Katayama T
线粒体是动态的细胞器，响应细胞外刺激而发生变化。这些变化对于正常的线粒体/细胞功能至关重要，并由促进融合和裂变的两种拮抗途径之间的紧密平衡控制。虽然一些分子已被确定介导线粒体融合和裂变过程，潜在的机制尚不清楚。肿瘤坏死因子受体相关蛋白1 （TRAP1）是调节多种线粒体功能的线粒体分子。在这里，我们研究了TRAP1在形态调控中的作用。稳定的TRAP1敲低细胞线粒体形态异常，我们观察到动力蛋白相关蛋白1 （Drp1）和线粒体裂变因子（Mff），线粒体裂变蛋白显著降低。在两种不同的细胞系SH-SY5Y神经母细胞瘤细胞和KNS-42胶质瘤细胞中短暂敲低TRAP1也获得了类似的结果。然而，TRAP1敲低并不影响融合蛋白的表达水平。在用蛋白酶体抑制剂MG132治疗后，Drp1和Mff蛋白水平的降低得以恢复。这些结果表明，TRAP1调节了线粒体的裂变蛋白表达，控制了线粒体的融合/裂变，从而影响了线粒体/细胞功能。
Mitochondria are dynamic organelles that change in response to extracellular stimuli. These changes are essential for normal mitochondrial/cellular function and are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Although some molecules have been identified to mediate the mitochondrial fusion and fission process, the underlying mechanisms remain unclear. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecule that regulates a variety of mitochondrial functions. Here, we examined the role of TRAP1 in the regulation of morphology. Stable TRAP1 knockdown cells showed abnormal mitochondrial morphology, and we observed significant decreases in dynamin-related protein 1 (Drp1) and mitochondrial fission factor (Mff), mitochondrial fission proteins. Similar results were obtained by transient knockdown of TRAP1 in two different cell lines, SH-SY5Y neuroblastoma cells and KNS-42 glioma cells. However, TRAP1 knockdown did not affect expression levels of fusion proteins. The reduction in Drp1 and Mff protein levels was rescued following treatment with the proteasome inhibitor MG132. These results suggest that TRAP1 regulates the expression of fission proteins and controls mitochondrial fusion/fission, which affects mitochondrial/cellular function.
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影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
DOI：
10.1080/10253890701314863
发表时间：
2007-11-01
影响因子：
2.3
作者：
Gesualdi, N. Montesano;Chirico, G.;Esposito, F.
通讯作者：
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影响因子：
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作者：
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通讯作者：
Schulz JB
影响因子：
11.8
作者：
Cassidy-Stone, Ann;Chipuk, Jerry E.;Nunnari, Jodi
通讯作者：
Nunnari, Jodi
影响因子：
4.8
作者：
James, DI;Parone, PA;Martinou, JC
通讯作者：
Martinou, JC