The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondria stressor rotenone
The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondria stressor rotenone
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DOI：
10.1016/j.yexcr.2012.07.004
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发表时间：
2012-10-15
影响因子：
3.7
通讯作者：
Chiaramello, Anne
中科院分区：
文献类型：
--
作者：
Baxter, Kristin Kathleen;Uittenbogaard, Martine;Chiaramello, Anne
如何以及哪些神经元特异性转录因子使线粒体生物发生和生物能量学适应神经元细胞发育的需要，这一基本问题在很大程度上仍未得到探索。在这项研究中，我们报告说，神经源性碱性螺旋-环-螺旋转录因子NeuroD 6具有线粒体生物合成的特性，通过放大线粒体DNA含量和TFAM表达水平，线粒体，生物合成的关键调节。在神经元祖细胞样PC 12-NEUROD 6细胞中，NeuroD 6介导的线粒体生物发生增加伴随着线粒体生物能功能的增强，包括电子传递链呼吸复合物的特定亚基的表达水平增加，线粒体膜电位和产生的ATP水平升高。氧化磷酸化。因此。NeuroD 6增强PC 12-NEUROD 6细胞的生物能量能力，以产生能量储备，从而赋予对线粒体应激物鱼藤酮的耐受性。我们发现NeuroD 6在鱼藤酮治疗过程中诱导了一种适应性生物能量反应，包括维持线粒体膜电位和ATP水平，同时保护肌动蛋白网络。总之，我们的研究结果支持这样的概念，即NeuroD 6在调节和协调神经元分化的发生中起着整合作用，获得足够的线粒体质量和能量能力，以确保能量需求事件，如细胞骨架重塑，质膜扩张和生长锥形成。(c)2012 Elsevier Inc. All rights reserved.
The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondria, biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced. by oxidative phosphorylation. Thus. NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. (c) 2012 Elsevier Inc. All rights reserved.