INSERM UMR 1141, Bâtiment Ecran, Hôpital Robert Debré, 48 Boulevard Serurier, 75019 Paris, France.
INSERM UMR 1141, Bâtiment Ecran, Hôpital Robert Debré, 48 Boulevard Serurier, 75019 Paris, France.
FEBS Lett. 2014 May 2;588(9):1832-8. doi: 10.1016/j.febslet.2014.03.046. Epub 2014 Apr 6.
Mammalian complex I is composed of fourteen highly conserved core subunits and additional thirty subunits acquired in the course of evolution. At present, the function of the majority of these supernumerary subunits is poorly understood. In this work, we have studied NDUFA3, NDUFA5 and NDUFA12 supernumerary subunits to gain insight into their role in CI activity and biogenesis. Using human cell lines in which the expression of these subunits was knocked down with miRNAs, we showed that they are necessary for the formation of a functional holoenzyme. Analysis of the assembly intermediates in mitochondria depleted for these subunits further suggested that they are required for assembly and/or stability of the electron transferring Q module in the peripheral arm of the CI.
哺乳动物复合物 I 由 14 个高度保守的核心亚基和在进化过程中获得的另外 30 个亚基组成。目前，这些多余亚基的大多数功能仍不清楚。在这项工作中，我们研究了 NDUFA3、NDUFA5 和 NDUFA12 多余亚基，以深入了解它们在 CI 活性和生物发生中的作用。我们使用人类细胞系，用 miRNA 敲低这些亚基的表达，结果表明它们是形成功能性全酶所必需的。对这些亚基耗尽的线粒体中组装中间体的分析进一步表明，它们对于 CI 外周臂中电子传递 Q 模块的组装和/或稳定性是必需的。
