More than just a ticket canceller: The mitochondrial processing peptidase tailors complex precursor proteins at internal cleavage sites

Jana Friedl, Michael R. Knopp, Carina Groh, Eyal Paz, Sven B. Gould, Johannes M. Herrmann, Felix Boos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Most mitochondrial proteins are synthesized as precursors that carry N-terminal presequences. After they are imported into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase (MPP). Using the mitochondrial tandem protein Arg5,6 as a model substrate, we demonstrate that MPP has an additional role in preprotein maturation, beyond the removal of presequences. Arg5,6 is synthesized as a polyprotein precursor that is imported into mitochondria and subsequently separated into two distinct enzymes. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor at its N-terminus and at an internal site. The peculiar organization of Arg5,6 is conserved across fungi and reflects the polycistronic arginine operon in prokaryotes. MPP cleavage sites are also present in other mitochondrial fusion proteins from fungi, plants, and animals. Hence, besides its role as a "ticket canceller"for removal of presequences, MPP exhibits a second conserved activity as an internal processing peptidase for complex mitochondrial precursor proteins.

Original languageEnglish
Pages (from-to)2657-2668
Number of pages12
JournalMolecular Biology of the Cell
Volume31
Issue number24
DOIs
StatePublished - 15 Nov 2020

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