Mitochondrial Intermediate Peptidase (MIPEP)

The MIPEP open reading frame encodes a 713-amino acid protein that is 92% homologous to rat MIP and 54% homologous to yeast MIP. the 2.4-kb mRNA is differentially expressed in human tissues, with highest levels in heart, skeletal muscle, and pancreas, 3 organ systems that are frequently affected in OXPHOS disorders.YMIP is activated by ferrous iron in vitro, and loss of YMIP activity leads to mitochondrial iron depletion, suggesting that YMIP is part of a feedback loop in which iron stimulates maturation of YMIP substrates and this in turn promotes mitochondrial iron uptake. Consistent with this suggestion, YMIP is active and promotes mitochondrial iron accumulation in a mutant lacking the yeast frataxin homolog, while genetic inactivation of YMIP in this mutant leads to a 2-fold reduction in mitochondrial iron levels.