CLONING, EXPRESSION, AND CHROMOSOMAL ASSIGNMENT OF THE HUMAN MITOCHONDRIAL INTERMEDIATE PEPTIDASE GENE (MIPEP)

The mitochondrial intermediate peptidase of Saccharomyces cerevisiae ( YMIP) is a component of the yeast mitochondrial protein import machine ry critically involved in the biogenesis of the oxidative phosphorylat ion (OXPHOS) system. This leader peptidase removes specific octapeptid es from the amino terminus of nuclear-encoded OXPHOS subunits and comp onents of the mitochondrial genetic apparatus. To address the biologic role of the human peptidase [MIPEP gene, HMIP polypeptide], we have i nitiated its molecular and functional characterization. A full-length cDNA was isolated by screening a human liver library using a rat MIP ( RMIP) cDNA as a probe. The encoded protein contained a typical mitocho ndrial leader peptide and showed 92 and 54% homology to RMIP and YMIP, respectively. A survey of human mitochondrial protein precursors reve aled that, similar to YMIP, HMIP is primarily involved in the maturati on of OXPHOS-related proteins. Northern analysis showed that the MIPEP gene is differentially expressed in human tissues, with the highest l evels of expression in the heart, skeletal muscle, and pancreas, three organ systems that are frequently affected in OXPHOS disorders. Using fluorescence in situ hybridization, the MIPEP locus was assigned to 1 3q12. This information offers the possibility of testing the potential involvement of HMIP in the pathophysiology of nuclear-driven OXPHOS d isorders. (C) 1997 Academic Press.