Mitochondrial Intermediate Peptidase (MIPEP) is a nuclear gene encoding a metalloprotease which is required for processing precursor mitochondrial proteins. Cytosolic proteins bound for mitochondria exhibit an N-terminal sequence that is essential for translocation and import into the organelle; this sequence is removed by a peptidase in the mitochondrion. A group of these proteins undergo a second processing step in which MIPEP excises an additional 8 amino acid peptide fragment before a mature stable protein is formed. MIPEP activity is stimulated by divalent cations and is involved in maturing proteins involved in oxidative phosphorylation; its function is essential to mitochondrial biogenesis and ATP production.
MIPEP dysfunction causes Combined Oxidative Phosphorylation Deficiency 31. Functional studies on a homologous yeast protein additionally indicate a role of the protease in mitochondrial iron homeostasis, therefore it is thought to be implicated in Friedrich’s Ataxia. A significant association between MIPEP variants and myopia has also been established.