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小鼠肺脏在出生后发育过程中线粒体形态和呼吸链复合物的差异变化。

Differential Alterations of the Mitochondrial Morphology and Respiratory Chain Complexes during Postnatal Development of the Mouse Lung.

机构信息

Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, Justus Liebig University, Giessen, Germany.

Department of Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen, Germany.

出版信息

Oxid Med Cell Longev. 2017;2017:9169146. doi: 10.1155/2017/9169146. Epub 2017 Dec 19.

Abstract

Mitochondrial biogenesis and adequate energy production in various organs of mammals are necessary for postnatal adaptation to extrauterine life in an environment with high oxygen content. Even though transgenic mice are frequently used as experimental models, to date, no combined detailed molecular and morphological analysis on the mitochondrial compartment in different lung cell types has been performed during postnatal mouse lung development. In our study, we revealed a significant upregulation of most mitochondrial respiratory complexes at protein and mRNA levels in the lungs of P15 and adult animals in comparison to newborns. The majority of adult animal samples showed the strongest increase, except for succinate dehydrogenase protein (SDHD). Likewise, an increase in mRNA expression for mtDNA transcription machinery genes (, , , and ), mitochondrially encoded RNA ( and mt), and the nuclear-encoded mitochondrial DNA polymerase (POLG) was observed. The biochemical and molecular results were corroborated by a parallel increase of mitochondrial number, size, cristae number, and complexity, exhibiting heterogeneous patterns in distinct bronchiolar and alveolar epithelial cells. Taken together, our results suggest a specific adaptation and differential maturation of the mitochondrial compartment according to the metabolic needs of individual cell types during postnatal development of the mouse lung.

摘要

哺乳动物各种器官中线粒体的生物发生和充足的能量产生对于在高氧环境中适应宫外生活是必要的。尽管转基因小鼠经常被用作实验模型,但迄今为止,在小鼠肺发育过程中,尚未对不同肺细胞类型中线粒体区室进行过联合的详细分子和形态学分析。在我们的研究中,与新生儿相比,我们在 P15 和成年动物的肺部发现大多数线粒体呼吸复合物的蛋白和 mRNA 水平都显著上调。除琥珀酸脱氢酶蛋白(SDHD)外,大多数成年动物样本的增加最为明显。同样,观察到 mtDNA 转录机制基因(、、、和)、线粒体编码 RNA(和 mt)以及核编码线粒体 DNA 聚合酶(POLG)的 mRNA 表达增加。生化和分子结果得到了线粒体数量、大小、嵴数量和复杂性平行增加的证实,在不同的细支气管和肺泡上皮细胞中表现出异质的模式。总之,我们的结果表明,在小鼠肺的出生后发育过程中,根据单个细胞类型的代谢需求,线粒体区室存在特定的适应和差异成熟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c252/5753018/27529a9aefee/OMCL2017-9169146.001.jpg

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