UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation

UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation
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DOI:
10.1007/s11626-007-9016-6
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发表时间:
2007-04-01
影响因子:
2.1
通讯作者:
Liu, Leyuan
Liu, Leyuan
中科院分区:
生物学4区
文献类型:
--
作者:
Moss, Tijuana N.;Vo, Amy;Liu, Leyuan

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线粒体是真核细胞的能量代谢中心,在细胞凋亡中起着重要作用。线粒体分布受微管骨架控制。线粒体的核周聚集是与某些类型的细胞死亡相关的特征之一。线粒体聚集的控制,特别是与细胞死亡事件的了解甚少。以前,我们确定遍在表达的转录本(UXT)作为线粒体相关的LRPPRC,一个多结构域的组织者,可能整合线粒体和微管细胞骨架与染色体重塑的潜在组成部分。在这里,我们表明,当在哺乳动物细胞中过表达时,绿色荧光蛋白标记的UXT(GFP-UXT)表现出四种类型的分布模式,与蛋白质水平成比例,并随时间增加。UXT最初分散在细胞核的胞质溶胶中,然后出现在点状的胞质溶胶点,然后强烈的核周聚集,最终侵入并破坏细胞核。GFP-UXT的点状胞浆聚集体与线粒体和LRPPRC的聚集体一致。我们的结论是,增加浓度的UXT有助于逐步聚集的线粒体和细胞死亡可能通过协会UXT与LRPPRC。
Mitochondria are the bioenergetic and metabolic centers in eukaryotic cells and play a central role in apoptosis. Mitochondrial distribution is controlled by the microtubular cytoskeleton. The perinuclear aggregation of mitochondria is one of the characteristics associated with some types of cell death. Control of mitochondrial aggregation particularly related to cell death events is poorly understood. Previously, we identified ubiquitously expressed transcript (UXT) as a potential component of mitochondrial associated LRPPRC, a multidomain organizer that potentially integrates mitochondria and the microtubular cytoskeleton with chromosome remodeling. Here we show that when overexpressed in mammalian cells, green fluorescent protein-tagged UXT (GFP-UXT) exhibits four types of distribution patterns that are proportional to the protein level, and increase with time. UXT initially was dispersed in the extranuclear cytosol, then appeared in punctate cytosolic dots, then an intense perinuclear aggregation that eventually invaded and disrupted the nucleus. The punctate cytosolic aggregates of GFP-UXT coincided with aggregates of mitochondria and LRPPRC. We conclude that increasing concentrations of UXT contributes to progressive aggregation of mitochondria and cell death potentially through association of UXT with LRPPRC.