Mitochondrial protein Preli-like is required for development of dendritic arbors and prevents their regression in the Drosophila sensory nervous system
Mitochondrial protein Preli-like is required for development of dendritic arbors and prevents their regression in the Drosophila sensory nervous system
复制标题
DOI：
10.1242/dev.042135
复制
发表时间：
2009-11
期刊：
影响因子：
4.6
通讯作者：
A. Tsubouchi;T. Tsuyama;M. Fujioka;Haruyasu Kohda;Keiko Okamoto‐Furuta;T. Aigaki;T. Uemura
中科院分区：
文献类型：
--
作者：
A. Tsubouchi;T. Tsuyama;M. Fujioka;Haruyasu Kohda;Keiko Okamoto‐Furuta;T. Aigaki;T. Uemura
线粒体的动态形态变化取决于各种真核生物中融合和分裂的平衡，并且对线粒体活性至关重要。线粒体功能障碍已成为许多神经系统疾病（包括神经变性）的共同主题。然而，这种异常的线粒体活性如何导致神经退行性疾病仍然是未知的。在这里，我们表明，果蝇线粒体蛋白质类（Prel），一个保守的PRELI/MSF 1家族的成员，有助于线粒体结构的完整性，呼吸链复合物IV的活性和细胞ATP水平。当体内神经元中Prel功能受损时，细胞ATP水平降低，线粒体变得碎片化并稀疏地分布在树突和轴突中。值得注意的是，树突的乔木简化和缩小，可能是由于近端树突的断裂和终末分支的进行性收缩。相比之下，废除线粒体运输机械本身有一个不那么深刻的影响乔木形态建成。有趣的是，在野生型背景中，Drob-I（Debcl）（果蝇Bcl-2家族蛋白质）的过表达产生了使人联想到prel表型的树突表型。此外，表达的Drob-I拮抗剂Buffy在prel突变神经元基本上恢复了树突状表型。我们的观察表明，Prel依赖的线粒体活性调节是重要的生长和预防断裂的树突状分支。
Dynamic morphological changes in mitochondria depend on the balance of fusion and fission in various eukaryotes, and are crucial for mitochondrial activity. Mitochondrial dysfunction has emerged as a common theme that underlies numerous neurological disorders, including neurodegeneration. However, how this abnormal mitochondrial activity leads to neurodegenerative disorders is still largely unknown. Here, we show that the Drosophila mitochondrial protein Preli-like (Prel), a member of the conserved PRELI/MSF1 family, contributes to the integrity of mitochondrial structures, the activity of respiratory chain complex IV and the cellular ATP level. When Prel function was impaired in neurons in vivo, the cellular ATP level decreased and mitochondria became fragmented and sparsely distributed in dendrites and axons. Notably, the dendritic arbors were simplified and downsized, probably as a result of breakage of proximal dendrites and progressive retraction of terminal branches. By contrast, abrogation of the mitochondria transport machinery per se had a much less profound effect on the arbor morphogenesis. Interestingly, overexpression of Drob-1 (Debcl), a Drosophila Bax-like Bcl-2 family protein, in the wild-type background produced dendrite phenotypes that were reminiscent of the prel phenotype. Moreover, expression of the Drob-1 antagonist Buffy in prel mutant neurons substantially restored the dendritic phenotype. Our observations suggest that Prel-dependent regulation of mitochondrial activity is important for both growth and prevention of breakage of dendritic branches.