Mitochondrial ATAD3A regulates milk biosynthesis and proliferation of mammary epithelial cells from dairy cow via the mTOR pathway

Mitochondrial ATAD3A regulates milk biosynthesis and proliferation of mammary epithelial cells from dairy cow via the mTOR pathway
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DOI:
10.1002/cbin.10929
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发表时间:
2018-05-01
影响因子:
3.9
通讯作者:
Gao, Xuejun
Gao, Xuejun
中科院分区:
生物学4区
文献类型:
--
作者:
Chen, Dongying;Yuan, Xiaohan;Gao, Xuejun

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ATP酶家族AAA-domain containing protein 3A(ATAD 3A)是一种由核蛋白编码的线粒体膜蛋白,在细胞生长和代谢中起重要作用。ATAD 3A的作用机制尚未完全了解。本研究探讨了ATAD 3A对奶牛乳腺上皮细胞乳汁合成和增殖的调控作用。我们发现ATAD 3A定位于线粒体中,并且ATAD 3A的表达响应于细胞外刺激如氨基酸和激素而上调。我们观察到ATAD 3A正调控乳蛋白、脂肪和乳糖的生物合成以及细胞增殖。我们进一步揭示ATAD 3A促进mTOR、SREBP-1c和Cyclin D1的表达,并触发mTOR磷酸化。总之,我们的数据表明,ATAD 3A调节mTOR,SREBP-1c和细胞周期蛋白D1信号通路的牛奶生物合成和细胞增殖。
ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane protein, which is essential for cell growth and metabolism. The mechanism by which ATAD3A acts is still not fully understood. In this study, we explored the regulatory role of ATAD3A on milk biosynthesis and proliferation of bovine mammary epithelial cell. We showed that ATAD3A is localized in mitochondria and the expression of ATAD3A was up-regulated in response to extracellular stimuli such as amino acids and hormones. We observed that ATAD3A positively regulated milk protein, fat, and lactose biosynthesis, and cell proliferation. We further revealed that ATAD3A promoted the expressions of mTOR, SREBP-1c, and Cyclin D1, and triggers mTOR phosphorylation. In summary, our data reveal that ATAD3A regulates the mTOR, SREBP-1c, and Cyclin D1 signaling pathways for milk biosynthesis and cell proliferation.