Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I.

We report here the isolation, mapping, and genomic organization of the human NDUFA1 gene, which is a component of NADH:ubiquinone oxidoreductase (complex I). The NDUFA1 cDNA clone and associated genomic cosmid clones were isolated by reciprocal probing of an arrayed human heart cDNA library with a X-chromosome cosmid library and were mapped to Xq24. The NDUFA1 gene, which is highly expressed in human cardiac and skeletal muscle, has an open reading frame of 70 amino acids and shows 80% homology to the bovine MWFE subunit of complex I. By primer extension, the major and minor transcription initiation sites were identified, 99 and 141 nucleotides upstream of the translation initiator ATG, respectively. The NDUFA1 gene is composed of 3 exons and spans about 5.0 kb of genomic DNA. The 5' region of the NDUFA1 gene (approximately 450-bp fragment) lacks conventional TATA and CAAT boxes, but it contains several potential binding sites for transcription factors including SP-1, AP-2, NF1, NRF2-like, APRRE, CRE, MyoD1, CArG, MEF-2, and BRE.