MOLECULAR CHARACTERIZATION AND MUTATIONAL ANALYSIS OF THE HUMAN B17 SUBUNIT OF THE MITOCHONDRIAL RESPIRATORY-CHAIN COMPLEX I

Bovine NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain consists of about 36 nuclear-encoded subunits. We r eview the current knowledge of the 15 human complex I subunits cloned so far, and report the 598-bp cDNA sequence, the chromosomal localizat ion and the tissue expression of an additional subunit, the B 17 subun it. The cDNA open reading frame of B17 comprises 387 bp and encodes a protein of 128 amino acids (calculated M-r 15.5 kDa). There is 82.7% a nd 78.1% homology, respectively, at the cDNA and amino acid level with the bovine counterpart. The gene of the B17 subunit has been mapped t o chromosome 2. Multiple-tissue dotblots showed ubiquitous expression of the mRNA with relatively higher expression in tissues known for the ir high energy demand. Of these, kidney showed the highest expression. Mutational analysis of the subunit revealed no mutations or polymorph isms in 20 patients with isolated enzymatic complex I deficiency in cu ltured skin fibroblasts.