E2F1通过与启动子结合来激活MFN2表达，并减少HeLa细胞中的线粒体裂变和线粒体。,The FEBS Journal

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E2F1通过与启动子结合来激活MFN2表达，并减少HeLa细胞中的线粒体裂变和线粒体。
The FEBS Journal ( IF 5.5 ) Pub Date : 2019-07-22 , DOI: 10.1111/febs.14980
Sudha Bucha ₁ , Debashis Mukhopadhyay ₂ , Nitai Pada Bhattacharyya ₁

Affiliation

Mitofusin-2（MFN2）主要参与线粒体融合，并参与多种生物学过程。几篇报道表明，MFN2是不同miRNA的靶标。但是，尚未对MFN2的转录调控进行深入研究。为了深入了解MFN2的转录调控，我们外源表达E2F转录因子1（E2F1），并观察到它通过结合其推定的启动子区域增加了MFN2的内源性表达。尽管显示E2F1的水平在细胞周期中发生变化，但MFN2及其调节剂SP1的表达在整个不同阶段均未发生变化，这表明E2F1以细胞周期独立的方式调节MFN2。在E2F1表达减少的细胞周期阶段，SP1可能在其位置调节MFN2的表达。我们表明，E2F1和SP1在S期以及E2F1过表达的细胞中以复合物的形式存在于MFN2的启动子上，这表明它们可能协同调节MFN2的表达。此外，我们发现E2F1可能通过调节MFN2来调节线粒体融合和线粒体。生物信息学分析表明，E2F1的几个潜在靶标位于线粒体中，并且与自噬有关。总的来说，这些数据将E2F1-MFN2轴确定为线粒体形态和线粒体的调节剂，提示了线粒体疾病的潜在治疗靶标。提示它们可能协同调节MFN2的表达。此外，我们发现E2F1可能通过调节MFN2来调节线粒体融合和线粒体。生物信息学分析表明，E2F1的几个潜在靶标位于线粒体中，并与自噬有关。总的来说，这些数据将E2F1-MFN2轴确定为线粒体形态和线粒体的调节剂，提示了线粒体疾病的潜在治疗靶标。提示它们可能协同调节MFN2的表达。此外，我们发现E2F1可能通过调节MFN2来调节线粒体融合和线粒体。生物信息学分析表明，E2F1的几个潜在靶标位于线粒体中，并与自噬有关。总的来说，这些数据将E2F1-MFN2轴确定为线粒体形态和线粒体的调节剂，提示了线粒体疾病的潜在治疗靶标。

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E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells.

Mitofusin-2 (MFN2) is primarily involved in mitochondrial fusion and participates in diverse biological processes. Several reports show that MFN2 is a target of different miRNAs; however, the transcriptional regulation of MFN2 has not been extensively studied. To gain insight into the transcriptional regulation of MFN2, we expressed E2F transcription factor 1 (E2F1) exogenously and observed that it increased the endogenous expression of MFN2 by binding to its putative promoter region. Although the levels of E2F1 were shown to vary during the cell cycle, the expression of MFN2 and its regulator SP1 did not change throughout the different phases, suggesting that E2F1 regulates MFN2 in a cell-cycle-independent manner. In the cell-cycle phases, where the expression of E2F1 was reduced, SP1 might act in its place to regulate the expression of MFN2. We showed that E2F1 and SP1 are present as a complex on the promoter of MFN2 during the S-phase as well as in E2F1 overexpressing cells, suggesting that they may regulate the expression of MFN2 synergistically. Furthermore, we found that E2F1 modulated mitochondrial fusion and mitophagy, likely through regulation of MFN2. Bioinformatic analysis revealed that several potential targets of E2F1 are localized in mitochondria and associated with autophagy. Collectively, these data identify the E2F1-MFN2 axis as a regulator of mitochondrial morphology and mitophagy, suggesting a potential therapeutic target for the treatment of mitochondrial disorders.

更新日期：2019-07-22

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