Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation
Nuclear-encoded mitochondrial ribosomal proteins are required to initiate gastrulation
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DOI：
10.1242/dev.188714
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发表时间：
2020-05-01
期刊：
影响因子：
4.6
通讯作者：
Mager, Jesse
中科院分区：
文献类型：
--
作者：
Cheong, Agnes;Archambault, Danielle;Mager, Jesse
线粒体对于能量产生至关重要，尽管它们有自己的基因组，但细胞器的正常功能需要许多核编码的线粒体核糖体蛋白 (MRP)。尽管 MRP 突变与人类疾病有关，但人们对其在发育过程中的作用知之甚少。这里介绍了 21 种核编码线粒体蛋白的无效表型以及 Mrp 基因 Mrpl3、Mrpl22、Mtpl44、Mrps18c 和 Mrps22 小鼠胚胎突变体的深入表征。每个 MRP 的丢失都会导致成功着床和卵柱形成，随后出现严重的发育迟缓，并且在胚胎第 7.5 天时无法启动原肠胚形成。鉴于有超过 70 个 MRP，并且表明几乎没有功能冗余，强大且相似的单敲除表型有些令人惊讶。代谢分析显示，Mrp 敲除胚胎产生的 ATP 明显低于对照，表明线粒体受损！功能。组织学和免疫荧光分析表明，Mrp 无效细胞的细胞器形态异常，并在 G2/M 检查点停滞。在许多不同的核编码线粒体蛋白敲除中观察到的几乎相同的原肠胚形成前表型暗示，不同的能量系统在哺乳动物发育过程中的特定时间点至关重要。本文有相关论文背后的人的采访。
Mitochondria are essential for energy production and although they have their own genome, many nuclear-encoded mitochondrial ribosomal proteins (MRPs) are required for proper function of the organelle. Although mutations in MRPs have been associated with human diseases, little is known about their role during development. Presented here are the null phenotypes for 21 nuclear-encoded mitochondrial proteins and in-depth characterization of mouse embryos mutant for the Mrp genes Mrpl3, Mrpl22, Mtpl44, Mrps18c and Mrps22. Loss of each MRP results in successful implantation and egg-cylinder formation, followed by severe developmental delay and failure to initiate gastrulation by embryonic day 7.5. The robust and similar single knockout phenotypes are somewhat surprising given there are over 70 MRPs and suggest little functional redundancy. Metabolic analysis reveals that Mrp knockout embryos produce significantly less ATP than controls, indicating compromised mitochondria! function. Histological and immunofluorescence analyses indicate abnormal organelle morphology and stalling at the G2/M checkpoint in Mrp null cells. The nearly identical pre-gastrulation phenotype observed for many different nuclear-encoded mitochondrial protein knockouts hints that distinct energy systems are crucial at specific time points during mammalian development.This article has an associated The people behind the papers' interview.