Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes.
Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes.
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DOI：
10.1371/journal.pone.0113330
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Porter GA Jr
中科院分区：
文献类型：
--
作者：
Beutner G;Eliseev RA;Porter GA Jr
真核细胞中线粒体以ATP的形式提供能量。然而，在胚胎心脏发育过程中，线粒体何时能够实现这一功能尚不清楚。为了评估这一点，我们测量了线粒体耗氧量和电子传递链（ETC）复合物（Cx） 1和2的活性，并使用免疫沉淀法跟踪线粒体超复合物的产生。我们发现，在胚胎期(E) 9.5的小鼠胚胎心脏中，线粒体ETC活性和氧化磷酸化（OXPHOS）不偶联，即使复合物存在。我们发现ETC的Cx-1能够接受来自克雷布斯循环的电子，但是专门测量流向泛醌或Cx-3的电子流的酶分析显示，在胚胎早期阶段没有活性。在E11.5时，线粒体在功能上显得更加成熟；ETC活性和OXPHOS偶联并响应ETC抑制剂。此外，含有Cx-1、-3和-4、泛醌和细胞色素c的高效呼吸超复合物的组装开始于E11.5，正是Cx-1功能激活的时间。在E13.5时，胚胎心脏线粒体的ETC活性和OXPHOS与成人线粒体没有区别。综上所述，我们的数据表明，在E9.5和E11.5之间，胚胎心脏的线粒体发生了巨大的变化，由于复合物1的激活和超复合物的形成，导致OXPHOS增加。
Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes.
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影响因子：
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