Complex I (CI) is the largest enzyme of the mitochondrial respiratory chain and its defects are the main cause of mitochondrial disease. To understand the mechanisms regulating the extremely intricate biogenesis of this fundamental bioenergetic machine, we analyzed the structural and functional consequences of the ablation of NDUFS3, a non-catalytic core subunit. We prove that in diverse mammalian cell types a small amount of functional CI can still be detected in the complete absence of NDUFS3. In addition, we have determined the dynamics of CI disassembly when the amount of NDUFS3 is gradually decreased. The process of degradation of the complex occurs in a hierarchical and modular fashion where the ND4-module remains stable and bound to TMEM126A. We have thus, uncovered the function of TMEM126A, the product of a disease gene causing recessive optic atrophy, as a factor necessary for the correct assembly and function of CI.

中文翻译：

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NDUFS3少复合物I的生物发生表明TMEM126A / OPA7是ND4模块的装配因子

复合物I（CI）是线粒体呼吸链中最大的酶，其缺陷是线粒体疾病的主要原因。为了了解调节这种基本生物能机器极其复杂的生物发生的机制，我们分析了NDUFS3（一种非催化性核心亚基）的消融的结构和功能后果。我们证明，在多种哺乳动物细胞类型中，在完全不存在NDUFS3的情况下仍可以检测到少量功能性CI。此外，我们确定了当NDUFS3的量逐渐减少时CI拆卸的动力学。复合物的降解过程以分级和模块化的方式进行，其中ND4模块保持稳定并绑定到TMEM126A。因此，我们发现了TMEM126A的功能，