SIM2s directed Parkin-mediated mitophagy promotes mammary epithelial cell differentiation.
SIM2s directed Parkin-mediated mitophagy promotes mammary epithelial cell differentiation.
复制标题
DOI：
10.1038/s41418-023-01146-9
复制
发表时间：
2023-06
影响因子：
12.4
通讯作者：
Porter, Weston W.
中科院分区：
文献类型：
--
作者：
Sanchez, Lilia;Epps, Jessica;Wall, Steven;McQueen, Cole;Pearson, Scott J.;Scribner, Kelly;Wellberg, Elizabeth A.;Giles, Erin D.;Rijnkels, Monique;Porter, Weston W.
功能分化的乳腺通过激活特定的保护机制来支持新生儿健康，从而适应对能量需求增加的极端压力水平。在这里，我们确定了乳腺癌抑制基因，一心一意2（SIM2S）作为一种新的调节线粒体自噬，这种应激反应的关键组成部分。使用组织特异性小鼠模型，我们发现Sim2的丢失降低了泌乳性能，而Sim2s的获得（过表达）增强和延长了泌乳性能和乳腺上皮细胞（MEC）的存活。使用MEC分化的体外模型，我们观察到SIM2s是Parkin介导的线粒体自噬所必需的，我们以前已经证明这是功能分化所必需的。在机制上，SIM2定位于线粒体以直接介导帕金线粒体负载。总之，我们的数据表明，SIM2通过线粒体自噬调节线粒体的快速循环，增强分化的MEC的功能和存活。
The functionally differentiated mammary gland adapts to extreme levels of stress from increased demand for energy by activating specific protective mechanisms to support neonatal health. Here, we identify the breast tumor suppressor gene, single-minded 2 s (SIM2s) as a novel regulator of mitophagy, a key component of this stress response. Using tissue-specific mouse models, we found that loss of Sim2 reduced lactation performance, whereas gain (overexpression) of Sim2s enhanced and extended lactation performance and survival of mammary epithelial cells (MECs). Using an in vitro model of MEC differentiation, we observed SIM2s is required for Parkin-mediated mitophagy, which we have previously shown as necessary for functional differentiation. Mechanistically, SIM2s localizes to mitochondria to directly mediate Parkin mitochondrial loading. Together, our data suggest that SIM2s regulates the rapid recycling of mitochondria via mitophagy, enhancing the function and survival of differentiated MECs.
登录
查看更多内容
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1126/science.aad2459
发表时间：
2015-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gong G;Song M;Csordas G;Kelly DP;Matkovich SJ;Dorn GW 2nd
通讯作者：
Dorn GW 2nd
影响因子：
8.8
作者：
Du, Jian;Gay, Melvin C. L.;Geddes, Donna T.
通讯作者：
Geddes, Donna T.
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
2.5
作者：
DePeters, Edward J.;Hovey, Russell C.
通讯作者：
Hovey, Russell C.