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The mitochondrial processing peptidase: Function and specificity

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Abstract

Targeting signals of mitochondrial precursors are cleaved in the matrix during or after import by the mitochondrial processing peptidase (MPP). This enzyme consists of two nonidenticalα- andβ-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 cytochromebc 1 complex. MPP is a metalloendopeptidase which has been classified as a member of the pitrilysin family on the basis of the HXXEHX76E zinc-binding motif present inβ-MPP. Both subunits of MPP are required for processing activity. Theα-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequence, presents the presequence toβ-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized peptides corresponding to mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals seem to be distinct, although the two signals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mimetic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence byα-MPP tolerates a high degree of mutations of the presequence.α-MPP may present a degenerated cleavage site motif toβ-MPP in an accessible conformation for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.

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  1. Laboratoire d'Ingéniérie des Systèmes Macromoléculaires, Institut de Biologie Structurale et Microbiologie, CNRS, 31 chemin Joseph Aiguier, F-13402, Marseille Cedex 20, (France)

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Luciano, P., Géli, V. The mitochondrial processing peptidase: Function and specificity. Experientia 52, 1077–1082 (1996). https://doi.org/10.1007/BF01952105

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