Cloning, expression, and chromosomal assignment of the human mitochondrial intermediate peptidase gene (MIPEP)

Genomics. 1997 Mar 15;40(3):493-6. doi: 10.1006/geno.1996.4586.

Abstract

The mitochondrial intermediate peptidase of Saccharomyces cerevisiae (YMIP) is a component of the yeast mitochondrial protein import machinery critically involved in the biogenesis of the oxidative phosphorylation (OXPHOS) system. This leader peptidase removes specific octapeptides from the amino terminus of nuclear-encoded OXPHOS subunits and components of the mitochondrial genetic apparatus. To address the biologic role of the human peptidase [MIPEP gene, HMIP polypeptide], we have initiated 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 mitochondrial leader peptide and showed 92 and 54% homology to RMIP and YMIP, respectively. A survey of human mitochondrial protein precursors revealed that, similar to YMIP, HMIP is primarily involved in the maturation of OXPHOS-related proteins. Northern analysis showed that the MIPEP gene is differentially expressed in human tissues, with the highest levels 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 13q12. This information offers the possibility of testing the potential involvement of HMIP in the pathophysiology of nuclear-driven OXPHOS disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Chromosomes, Human, Pair 13*
  • Cloning, Molecular
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Metalloendopeptidases / genetics*
  • Molecular Sequence Data
  • Rats

Substances

  • Metalloendopeptidases
  • mitochondrial intermediate peptidase

Associated data

  • GENBANK/U80034