The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, Harbin, 150030, China.
Cell Biol Int. 2018 May;42(5):533-542. doi: 10.1002/cbin.10929. Epub 2018 Jan 24.
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.
三磷酸腺苷酶家族 AAA 结构域包含蛋白 3A(ATAD3A)是一种核编码的线粒体膜蛋白,对细胞生长和代谢至关重要。ATAD3A 的作用机制尚不完全清楚。在这项研究中,我们探讨了 ATAD3A 对奶牛乳腺上皮细胞乳生物合成和增殖的调节作用。结果表明,ATAD3A 定位于线粒体中,其表达在氨基酸和激素等细胞外刺激下上调。我们观察到 ATAD3A 正向调节乳蛋白、脂肪和乳糖的生物合成以及细胞增殖。进一步研究表明,ATAD3A 可促进 mTOR、SREBP-1c 和 Cyclin D1 的表达,从而触发 mTOR 磷酸化。综上所述,本研究数据揭示了 ATAD3A 通过调节 mTOR、SREBP-1c 和 Cyclin D1 信号通路来调节乳生物合成和细胞增殖。