对水产业造成巨大损失的重要原因是缺氧导致的鱼类大量死亡，虽然人们对鱼类低氧适应机制进行了一些报道，但关于miRNAs的研究较少。在前期研究中我们发现miR-462-731簇为硬骨鱼类特有，受低氧诱导表达；功能分析初步显示该基因簇可能与Akt-FoxO通路有关，参与调节线粒体功能，那么miR-462-731是否通过Akt-FoxO通路调控线粒体功能进而参与氧的利用？本项目拟从线粒体氧化磷酸化、能量代谢及形态结构等方面研究团头鲂miR-462-731对线粒体功能的影响途径；通过靶标检测、基因过表达及沉默等实验分析Akt-FoxO通路在miR-462-731调节线粒体功能中的作用；在机体水平，利用该基因簇敲除模型从氧的运输和利用角度解析其在低氧调节中的分子机制。研究结果将有助于系统了解鱼类低氧适应的分子调控机制，还可为鱼类耐低氧品种的培育提供一定的理论基础。

One important reason for causing enormous economic losses in aquaculture is that a large amount of fish die due to hypoxia. Some regulation mechanisms about fish hypoxia adaptation have been reported, but it is limited about studies of miRNA function in fish hypoxia adaptation. Our previous studies showed that hypoxia induced the expression of teleost-specific miR-462 and miR-731 (located in the same gene cluster, namely miR-462-731). Function analysis revealed that the miRNA cluster was probably related with the Akt-FoxO pathway, and involved in regulation of mitochondrial function. Whether was miR-462-731 involved in mitochondrial function by the Akt-FoxO pathway to further affect oxygen utilization? Therefore, in the present study, effects of Megalobrama amblycephala miR-462-731 on mitochondrial biological functions will be investigated based on detection of mitochondrial oxidative phosphorylation, energy metabolism and morphological structure, etc. Function of the Akt-FoxO pathway mediated by miR-462-731 in mitochondrial responses will also be analyzed by miRNA target identification, gene overexpression and silencing etc. In addition, regulation mechanisms of the miRNA cluster in hypoxia response will be elucidated from the point of oxygen transportation and utilization using miR-462-731 knockout mutants as a model. Our results will not only contribute to systematically understand molecular regulatory mechanisms of fish hypoxia adaptation, but provide some theory evidences for breeding of hypoxia tolerant fish.