USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Houston, TX 77030, USA.
Physiol Genomics. 2011 Mar 29;43(6):271-85. doi: 10.1152/physiolgenomics.00133.2010. Epub 2010 Dec 28.
The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypothesis tested was that changes in mammary cell mitochondrial biogenesis and function during lactation would be accounted for by coordinated changes in the proteins of the electron transport chain and that some of these proteins might be linked by their expression patterns to PPARGC1α and AMP kinase. The mitochondrial proteome was studied along with markers of mitochondrial biogenesis and function in mammary tissue collected from mice over the course of a single prolonged lactation cycle. Mammary tissue concentrations of AMP and ADP were increased (P < 0.05) during early lactation and then declined with prolonged lactation. Similar changes were also observed for mitochondrial ATP synthesis activity, mitochondrial mass and DNA copy number. Analysis of the mammary cell mitochondrial proteome identified 244 unique proteins. Of these, only two proteins of the electron transport chain were found to increase during early lactation. In contrast, coordinated changes in numerous electron transport chain proteins were observed both during mid- and late lactation. There were six proteins that could be directly linked to PPARGC1α through network analysis. Abundance of PPARGC-1α and phosphorylation of AMP kinase was highest on day 2 postpartum. The results suggest that the increases in mammary mitochondria ATP synthesis activity during early lactation results from changes in only a limited number proteins. In addition, decreases in a handful of proteins linked to lipid oxidation could be temporally linked to decreases in PPARGC1α and phospho-AMP kinase suggesting potential roles for these proteins in coordinating mammary gland metabolism during early lactation.
哺乳期乳腺细胞中线粒体生物发生和功能的调节知之甚少。本研究的目的是使用蛋白质组学来研究哺乳期乳腺细胞中线粒体功能的时间变化与构成该细胞器的蛋白质变化之间的关系。测试的假设是，哺乳期乳腺细胞中线粒体生物发生和功能的变化将与电子传递链蛋白的协调变化有关，并且其中一些蛋白可能通过其表达模式与 PPARGC1α 和 AMP 激酶相关。研究了线粒体蛋白质组以及在单个延长哺乳期期间从小鼠乳腺组织中收集的线粒体生物发生和功能的标志物。在早期哺乳期，乳腺组织中的 AMP 和 ADP 浓度增加（P < 0.05），然后随着哺乳期的延长而下降。线粒体 ATP 合成活性、线粒体质量和 DNA 拷贝数也观察到类似的变化。对乳腺细胞线粒体蛋白质组的分析鉴定了 244 种独特的蛋白质。其中，只有两种电子传递链蛋白在早期哺乳期增加。相比之下，在中期和晚期哺乳期观察到许多电子传递链蛋白的协调变化。通过网络分析可以直接与 PPARGC1α 相关的有 6 种蛋白质。PPARGC-1α 的丰度和 AMP 激酶的磷酸化在产后第 2 天最高。结果表明，早期哺乳期乳腺线粒体 ATP 合成活性的增加仅源于少数蛋白质的变化。此外，与脂质氧化相关的少数蛋白质的减少可能与 PPARGC1α 和磷酸化 AMP 激酶的减少在时间上相关，这表明这些蛋白质在协调早期哺乳期乳腺代谢方面可能发挥作用。
