Mitochondrial processing peptidases

Abstract

Three peptidases are responsible for the proteolytic processing of both nuclearly and mitochondrially encoded precursor polypeptides targeted to the various subcompartments of the mitochondria. Mitochondrial processing peptidase (MPP) cleaves the vast majority of mitochondrial proteins, while inner membrane peptidase (IMP) and mitochondrial intermediate peptidase (MIP) process specific subsets of precursor polypeptides. All three enzymes are structurally and functionally conserved across species, and their human homologues begin to be recognized as potential players in mitochondrial disease.

Smac/DIABLO and cytochrome c are released from mitochondria through a similar mechanism during UV-induced apoptosis

“…In general, most proteins destined for the intermembrane space are initially synthesized as larger precursor polypeptides carrying two signal sequences at N-terminal, a matrix-targeting signal followed by an intermembrane space-sorting signal. 28,29 After the protein is imported into the mitochondrial matrix, its matrix-targeting signal is cleaved by the mitochondrial processing peptidase. Then, the intermembrane space-sorting signal is removed by the inner membrane peptidase, and the mature polypeptide is released into the intermembrane space.…”

The direct route: a simplified pathway for protein import into the mitochondrion of trypanosomes

“…Mitochondrial targeting information is coded in hydrophobic and basic residues, often present at the N-terminus in the form of a basic, amphipathic helix referred to as a presequence. Such presequences are 30-50 residues long and are proteolytically removed by peptidases: the matrix processing peptidase (MPP) or inner membrane located peptidase (IMP), once the imported protein has reached its final destination within the mitochondrion [2,35,41].…”

“…The OXA complex that assists assembly of at least some of the inner membrane proteins that have multiple a-helical transmembrane segments is derived from the bacterial protein YidC [34]. The inner membrane-associated protease (IMP) that processes signal sequences from proteins inserted into the inner membrane is derived from the bacterial signal peptidase [35]. A core subunit of these complexes is present in T. brucei.…”

A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

“…77 Therefore, it is probably executed by one of the two proteases that typically are responsible for the import of most IMM proteins, the mitochondrial processing peptidase (MPP) and the innermembrane peptidase (IMP). 83 The distal b-cleavage ( 77 SerkAla 78 ) is regulated through a mechanism of proteolysis requiring Parl activity supplied in trans: a catalytically inactive Parl is not subjected to b-cleavage unless wild-type Parl was co-expressed. 77 The identity of the matrix protease that cleaves Parl at the bcleavage site remains elusive.…”

“…74 b-cleavage appears to require strict sequence conservation, as it is blocked when any of the four residues surrounding the site of cleavage are changed in Glu residues ( 76 RSkAL 79 ). 77 Since proteases implicated in the import of mitochondrial proteins do not have sequence specificity requirements, 83 b-cleavage is thus unlikely mediated by a protease of the import machinery, such as MPP and IMP. As mentioned above, mAAA proteases could supply the proteolytic activity required for b-cleavage of Parl.…”