Mitochondrial complex I, a proton‐pumping NADH: ubiquinone oxidoreductase, is required for oxidative phosphorylation. However, the contribution of several human mutations to complex I deficiency is poorly understood. The unicellular alga Chlamydomonas reinhardtii was utilized to study complex I as, unlike in mammals, mutants with complete loss of the holoenzyme are viable. From a forward genetic screen for complex I‐deficient insertional mutants, six mutants exhibiting complex I deficiency with assembly defects were isolated. Chlamydomonas mutants isolated from our screens, lacking the subunits NDUFV2 and NDUFB10, were used to reconstruct and analyze the effect of two human mutations in these subunit‐encoding genes. The K209R substitution in NDUFV2, reported in Parkinson's disease patients, did not significantly affect the enzyme activity or assembly. The C107S substitution in the NDUFB10 subunit, reported in a case of fatal infantile cardiomyopathy, is part of a conserved C‐(X)₁₁‐C motif. The cysteine substitutions, at either one or both positions, still allowed low levels of holoenzyme formation, indicating that this motif is crucial for complex I function but not strictly essential for assembly. We show that the algal mutants provide a simple and useful platform to delineate the consequences of patient mutations on complex I function.

中文翻译：

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莱茵衣藻作为植物模型系统来研究线粒体复合物 I 功能障碍。


线粒体复合物 I 是一种质子泵 NADH：泛醌氧化还原酶，是氧化磷酸化所必需的。然而，几种人类突变对复合物 I 缺乏的影响尚不清楚。单细胞藻类莱茵衣藻被用来研究复合物 I，因为与哺乳动物不同，完全丧失全酶的突变体是可行的。通过对复合物 I 缺陷插入突变体的正向遗传筛选，分离出 6 个表现出复合物 I 缺陷和组装缺陷的突变体。从我们的筛选中分离出的缺乏 NDUFV2 和 NDUFB10 亚基的衣藻突变体被用来重建和分析这些亚基编码基因中两个人类突变的影响。据帕金森病患者报道，NDUFV2 中的 K209R 取代并未显着影响酶活性或组装。在致命性婴儿心肌病病例中报道的 NDUFB10 亚基中的 C107S 取代是保守的 C-(X) ₁₁ -C 基序的一部分。一个或两个位置的半胱氨酸取代仍然允许低水平的全酶形成，表明该基序对于复合物 I 功能至关重要，但对于组装而言并非严格必需。我们表明，藻类突变体提供了一个简单而有用的平台来描述患者突变对复合物 I 功能的影响。