GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH : Ubiquinone oxidoreductase (complex I)

The sequences of 42 subunits of NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria have been described previously. Seven are en coded by mitochondrial DNA, whereas the remaining 35 are nuclear gene produ cts imported into the organelle from the cytoplasm. An additional protein, which does not correspond to any previously known subunit of the complex I assembly, has now been detected. Denaturing gels of subcomplex Id, the hydr ophilic arm of complex I, clearly show a hitherto unidentified band, which was digested with trypsin and subjected to mass-spectrometric analysis to p rovide several peptide sequences, used in cDNA cloning and sequencing. Meas urement of the intact protein mass indicated that the N terminus is acetyla ted. The new complex I subunit (B16.6) is the bovine homolog of GRIM-19, th e product of a cell death regulatory gene induced by interferon-beta and re tinoic acid, thus providing a new link between the mitochondrion and its el ectron-transport chain and apoptotic cell death.