MYBL2 guides autophagy suppressor VDAC2 in the developing ovary to inhibit autophagy through a complex of VDAC2-BECN1-BCL2L1 in mammals.
MYBL2 guides autophagy suppressor VDAC2 in the developing ovary to inhibit autophagy through a complex of VDAC2-BECN1-BCL2L1 in mammals.
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DOI：
10.1080/15548627.2015.1040970
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发表时间：
2015
期刊：
影响因子：
13.3
通讯作者：
Zhou R
中科院分区：
文献类型：
--
作者：
Yuan J;Zhang Y;Sheng Y;Fu X;Cheng H;Zhou R
卵子发生对于哺乳动物雌性配子的产生至关重要。卵巢卵泡的总数在生命早期就已确定，并且卵巢卵母细胞的产生被认为在一生中停止。然而，卵子发生的分子机制，特别是卵巢自噬调节，仍然很大程度上未知。在这里，我们揭示了一条与发育中卵巢自噬抑制相关的重要 MYBL2-VDAC2-BECN1-BCL2L1 通路。转录因子 GATA1 和 MYBL2 可以结合并激活 Vdac2 启动子。 MYBL2 调节发育中卵巢中 VDAC2 的时空表达。引人注目的是，在VDAC2转基因猪（Sus scrofa/Ss）中，VDAC2通过抑制卵巢自噬发挥其功能。相比之下，Vdac2 敲除会促进自噬。此外，VDAC2 介导的自噬抑制依赖于其与 BECN1 和 BCL2L1 的相互作用来稳定 BECN1 和 BCL2L1 复合物，表明 VDAC2 作为该途径中的自噬抑制因子。我们的研究结果提供了 VDAC2、MYBL2、BECN1-BCL2L1 通路和发育中卵巢自噬抑制之间的功能联系，这与提高女性生育力有关。
Oogenesis is essential for female gamete production in mammals. The total number of ovarian follicles is determined early in life and production of ovarian oocytes is thought to stop during the lifetime. However, the molecular mechanisms underling oogenesis, particularly autophagy regulation in the ovary, remain largely unknown. Here, we reveal an important MYBL2-VDAC2-BECN1-BCL2L1 pathway linking autophagy suppression in the developing ovary. The transcription factors GATA1 and MYBL2 can bind to and activate the Vdac2 promoter. MYBL2 regulates the spatiotemporal expression of VDAC2 in the developing ovary. Strikingly, in the VDAC2 transgenic pigs (Sus scrofa/Ss), VDAC2 exerts its function by inhibiting autophagy in the ovary. In contrast, Vdac2 knockout promotes autophagy. Moreover, VDAC2-mediated autophagy suppression is dependent on its interactions with both BECN1 and BCL2L1 to stabilize the BECN1 and BCL2L1 complex, suggesting VDAC2 as an autophagy suppressor in the pathway. Our findings provide a functional connection among the VDAC2, MYBL2, the BECN1-BCL2L1 pathway and autophagy suppression in the developing ovary, which is implicated in improving female fecundity.