Mitochondrial biogenesis in the axons of vertebrate peripheral neurons.
Mitochondrial biogenesis in the axons of vertebrate peripheral neurons.
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DOI：
10.1002/dneu.20668
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发表时间：
2008-09-15
影响因子：
3
通讯作者：
Hollenbeck, Peter J.
中科院分区：
文献类型：
--
作者：
Amiri, Mandana;Hollenbeck, Peter J.
线粒体通过神经元中的调节运输广泛分布，但其生物发生位点仍不确定。大多数线粒体蛋白是在核基因组中编码的，有证据表明线粒体 DNA (mtDNA) 复制主要或完全发生在细胞体内。然而，人们也清楚核编码的线粒体蛋白可以在轴突中翻译，并且线粒体复制机制的组件也驻留在轴突中。我们直接评估了 mtDNA 复制是否可以发生在用 5-bromo-2'-deoxyuridine (BrdU) 标记的鸡外周神经元的轴突中。在与细胞体物理分离或细胞体和轴突之间的细胞器运输被破坏的轴突中，很大一部分线粒体DNA合成仍在继续。我们还通过免疫荧光或GFP-Drp1的表达检测了神经元中的线粒体裂变蛋白Drp1。它在大多数轴突线粒体上的存在和分布表明，相当数量的线粒体最近在轴突中经历了分裂。由于线粒体的形态是通过裂变和融合事件的平衡来维持的，因此我们要么通过 RNAi 抑制 Drp1 表达，要么过表达融合蛋白 Mfn1。这两种方法都会导致轴突中的线粒体明显更长，其中许多线粒体距离细胞体很远。这些数据表明线粒体可以在轴突内复制其 DNA、分裂和融合。因此，线粒体的生物发生并不局限于细胞体。
Mitochondria are widely distributed via regulated transport in neurons, but their sites of biogenesis remain uncertain. Most mitochondrial proteins are encoded in the nuclear genome, and evidence has suggested that mitochondrial DNA (mtDNA) replication occurs mainly or entirely in the cell body. However, it has also become clear that nuclear-encoded mitochondrial proteins can be translated in the axon and that components of the mitochondrial replication machinery reside there as well. We assessed directly whether mtDNA replication can occur in the axons of chick peripheral neurons labeled with 5-bromo-2′-deoxyuridine (BrdU). In axons that were physically separated from the cell body or had disrupted organelle transport between the cell bodies and axons, a significant fraction of mtDNA synthesis continued. We also detected the mitochondrial fission protein Drp1 in neurons by immunofluorescence or expression of GFP-Drp1. Its presence and distribution on the majority of axonal mitochondria indicated that a substantial number had undergone recent division in the axon. Because the morphology of mitochondria is maintained by the balance of fission and fusion events, we either inhibited Drp1 expression by RNAi or overexpressed the fusion protein Mfn1. Both methods resulted in significantly longer mitochondria in axons, including many at a great distance from the cell body. These data indicate that mitochondria can replicate their DNA, divide, and fuse locally within the axon; thus, the biogenesis of mitochondria is not limited to the cell body.
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影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
DOI：
10.1006/bbrc.1994.1603
发表时间：
1994-05-16
影响因子：
3.1
作者：
LARSSON, NG;OLDFORS, A;CLAYTON, DA
通讯作者：
CLAYTON, DA
影响因子：
16.2
作者：
Campbell, DS;Holt, CE
通讯作者：
Holt, CE
影响因子：
7.8
作者：
Davis, AF;Clayton, DA
通讯作者：
Clayton, DA
影响因子：
3.3
作者：
Koenig, E;Giuditta, A
通讯作者：
Giuditta, A