Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development
Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development
复制标题
线粒体融合与河马途径在果蝇发育过程中控制细胞增殖的交叉对话。
DOI：
10.1534/genetics.115.186445
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发表时间：
2016-08-01
期刊：
影响因子：
3.3
通讯作者：
Ge, Wanzhong
中科院分区：
文献类型：
--
作者：
Deng, Qiannan;Guo, Ting;Ge, Wanzhong
细胞增殖和组织生长依赖于动物发育过程中多种信号分子和途径的协调调节。以前的研究已经将线粒体功能与生长控制中的Hippo信号通路联系起来。然而，潜在的分子机制尚未完全理解。在这里，我们确定了果蝇线粒体内膜蛋白ChChd3作为一种新的调节组织生长。ChChd3的缺失导致组织生长不足和细胞增殖缺陷。ChChd3是线粒体融合所必需的，去除ChChd3会增加线粒体片段化。ChChd3是Hippo途径的另一个线粒体靶点，尽管它只是Hippo途径介导的过度生长所需的部分靶点。有趣的是，缺乏ChChd3导致在正常发育下Hippo活性失活，这也依赖于转录辅激活因子Yorkie（Yki）。此外，ChChd3的丢失诱导氧化应激并激活JNK通路。此外，其他线粒体融合成分Opa1或Marf的耗尽也会使Hippo通路失活。综上所述，我们认为线粒体融合和Hippo通路之间存在相互作用，这在果蝇的细胞增殖和组织稳态控制中至关重要。
Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila.