THE MITOCHONDRIAL PROCESSING PEPTIDASE - FUNCTION AND SPECIFICITY

Targeting signals of mitochondrial precursors are cleaved in the matri x during or after import by the mitochondrial processing peptidase (MP P). This enzyme consists of two nonidentical alpha- and beta-subunits each of molecular weight of about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in plants the enzyme is part of the cy tochrome bc(1) complex. MPP is a metalloendopeptidase which has been c lassified as a member of the pitrilysin family on the basis of the HXX EHX(76)E zinc-binding motif present in beta-MPP. Both subunits of MPP are required for processing activity. The alpha-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequen ce, presents the presequence to beta-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized pep tides corresponding to mitochondrial presequences. Matrix-targeting si gnals and MPP cleavage signals seem to be distinct, although the two s ignals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mime tic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence by alpha-MPP tolerates a h igh degree of mutations of the presequence. alpha-MPP may present a de generated cleavage site motif to beta-MPP in an accessible conformatio n for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.