Smeitink J A, Loeffen J L, Triepels R H, Smeets R J, Trijbels J M, van den Heuvel L P
Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Hospital Nijmegen, Geert Grooteplein 20, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Hum Mol Genet. 1998;7(10):1573-9. doi: 10.1093/hmg/7.10.1573.
The mitochondrial electron transport chain (mtETC) consists of four multi-subunit enzyme complexes. Complex I or NADH:ubiquinone oxidoreductase, the largest mtETC multisubunit complex, consists of approximately 41 subunits. Seven of these subunits are encoded by the mitochondrial genome, the remainder by the nuclear genome. Among the mitochondriocytopathies, complex I deficiencies are encountered frequently. Although some complex I deficiencies have been associated with mitochondrial DNA mutations, the genetic defect has not been elucidated in the majority of complex I-deficient patients. It is expected that many of these patients have mutations in the nuclear-encoded subunits of this complex, so vital for cellular energy production. After a brief summary of the current knowledge of complex I from cow, bacteria and fungi, this review presents the state of the art of the knowledge of the human nuclear-encoded complex I genes which, in the last 18 months, has made enormous progress. At present, the complete gene structure of four subunits and the cDNA structure of 18 of the 34 complex I nuclear-encoded subunits are known. Mapping of these subunits shows a random distribution over the chromosomes. The chromosomal localization is known for 14 complex I genes. Recently, the first mutation, a 5 bp duplication in the 18 kDa (AQDQ) subunit, has been reported. We expect that within 1 year all human nuclear-encoded complex I subunits will be cloned. Mutational analysis of these subunits is warranted in complex I-deficient patients and will not only be important for genetic counselling but will also extend the knowledge regarding the functional properties of the individual human complex I subunits.
线粒体电子传递链（mtETC）由四个多亚基酶复合物组成。复合物I即NADH：泛醌氧化还原酶，是最大的mtETC多亚基复合物，由大约41个亚基组成。其中7个亚基由线粒体基因组编码，其余由核基因组编码。在线粒体细胞病中，复合物I缺陷较为常见。虽然一些复合物I缺陷与线粒体DNA突变有关，但大多数复合物I缺陷患者的遗传缺陷尚未阐明。预计这些患者中的许多人在该复合物的核编码亚基中存在突变，而该复合物对细胞能量产生至关重要。在简要总结了目前关于牛、细菌和真菌中复合物I的知识后，本综述介绍了人类核编码复合物I基因的知识现状，在过去18个月中，这方面取得了巨大进展。目前，已知四个亚基的完整基因结构以及34个复合物I核编码亚基中18个的cDNA结构。这些亚基的定位显示在染色体上随机分布。已知14个复合物I基因的染色体定位。最近，报道了第一个突变，即18 kDa（AQDQ）亚基中的5 bp重复。我们预计在1年内将克隆所有人类核编码的复合物I亚基。对这些亚基进行突变分析对复合物I缺陷患者是必要的，这不仅对遗传咨询很重要，也将扩展关于单个人类复合物I亚基功能特性的知识。
