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

2020 ◽  
Author(s):  
Jana Friedl ◽  
Michael R. Knopp ◽  
Carina Groh ◽  
Eyal Paz ◽  
Sven B. Gould ◽  
...  
Keyword(s):  
Mitochondrial Matrix ◽  
Cleavage Sites ◽  
Arginine Biosynthesis ◽  
Mitochondrial Processing Peptidase ◽  
Precursor Proteins ◽  
Internal Site ◽  
Processing Peptidase ◽  
Polyprotein Precursor ◽  
Internal Processing ◽  
Additional Role

AbstractMost mitochondrial proteins are synthesized in the cytosol as precursors that carry N-terminal presequences. After import into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase MPP, giving rise to shorter mature proteins. 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 the mitochondrial matrix and subsequently separated into two distinct enzymes that function in arginine biogenesis. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor both at its N-terminus and at an internal site between the Arg5 and Arg6 parts. The peculiar organization and biogenesis of Arg5,6 is conserved across fungi and might preserve the mode of co-translational subunit association of the arginine biosynthesis complex of the polycistronic arginine operon in prokaryotic mitochondrial ancestors. Putative MPP cleavage sites are also present at the junctions in other mitochondrial fusion proteins from fungi, plants and animals. Our data suggest that, in addition to its role as “ticket canceller” for the removal of presequences, MPP exhibits a second, widely conserved activity as internal processing peptidase for complex mitochondrial precursor proteins.

scholarly journals Recognition and processing of a nuclear-encoded polyprotein precursor by mitochondrial processing peptidase

2005 ◽  
Vol 385 (3) ◽  
pp. 755-761 ◽  
Author(s):  
Tsutomu OSHIMA ◽  
Eiki YAMASAKI ◽  
Tadashi OGISHIMA ◽  
Koh-ichi KADOWAKI ◽  
Akio ITO ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Succinate Dehydrogenase ◽  
Cleavage Site ◽  
Essential Role ◽  
Mitochondrial Matrix ◽  
Inner Membrane ◽  
Mitochondrial Processing Peptidase ◽  
Large N ◽  
Processing Peptidase ◽  
Polyprotein Precursor

The nuclear-encoded protein RPS14 (ribosomal protein S14) of rice mitochondria is synthesized in the cytosol as a polyprotein consisting of a large N-terminal domain comprising preSDHB (succinate dehydrogenase B precursor) and the C-terminal RPS14. After the preSDHB–RPS14 polyprotein is transported into the mitochondrial matrix, the protein is processed into three peptides: the N-terminal prepeptide, the SDHB domain and the C-terminal mature RPS14. Here we report that the general MPP (mitochondrial processing peptidase) plays an essential role in processing of the polyprotein. Purified yeast MPP cleaved both the N-terminal presequence and the connector region between SDHB and RPS14. Moreover, the connector region was processed more rapidly than the presequence. When the site of cleavage between SDHB and RPS14 was determined, it was located in an MPP processing motif that has also been shown to be present in the N-terminal presequence. Mutational analyses around the cleavage site in the connector region suggested that MPP interacts with multiple sites in the region, possibly in a similar manner to the interaction with the N-terminal presequence. In addition, MPP preferentially recognized the unfolded structure of preSDHB–RPS14. In mitochondria, MPP may recognize the stretched polyprotein during passage of the precursor through the translocational apparatus in the inner membrane, and cleave the connecting region between the SDHB and RPS14 domains even before processing of the presequence.

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

2020 ◽  
Vol 31 (24) ◽  
pp. 2657-2668
Author(s):  
Jana Friedl ◽  
Michael R. Knopp ◽  
Carina Groh ◽  
Eyal Paz ◽  
Sven B. Gould ◽  
...  
Keyword(s):  
Cleavage Sites ◽  
Mitochondrial Processing Peptidase ◽  
Precursor Proteins ◽  
Processing Peptidase ◽  
Complex Precursor ◽  
Targeting Signals

The Mitochondrial processing peptidase (MPP) is well known for cleaving off N-terminal targeting signals from mitochondrial precursor proteins. Here we show that MPP also processes more complex precursors at internal cleavage sites, separating polyproteins into distinct functional enzymes. This function is conserved among eukaryotes.

scholarly journals Maturation of Mitochondrially Targeted Prx V Involves a Second Cleavage by Mitochondrial Intermediate Peptidase That Is Sensitive to Inhibition by H2O2

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 346
Author(s):  
Juhyun Sim ◽  
Jiyoung Park ◽  
Hyun Ae Woo ◽  
Sue Goo Rhee
Keyword(s):  
Short Form ◽  
Mitochondrial Matrix ◽  
Mitochondrial Processing Peptidase ◽  
Mouse Tissues ◽  
N Terminus ◽  
Mitochondrial Intermediate Peptidase ◽  
Subsequent Degradation ◽  
Processing Peptidase ◽  
Mitochondria Targeting ◽  
Over Time

Prx V mRNA contains two in-frame AUG codons, producing a long (L-Prx V) and short form of Prx V (S-Prx V), and mouse L-Prx V is expressed as a precursor protein containing a 49-amino acid N-terminal mitochondria targeting sequence. Here, we show that the N-terminal 41-residue sequence of L-Prx V is cleaved by mitochondrial processing peptidase (MPP) in the mitochondrial matrix to produce an intermediate Prx V (I-Prx V) with a destabilizing phenylalanine at its N-terminus, and further, that the next 8-residue sequence is cleaved by mitochondrial intermediate peptidase (MIP) to convert I-Prx V to a stabilized mature form that is identical to S-Prx V. Further, we show that when mitochondrial H2O2 levels are increased in HeLa cells using rotenone, in several mouse tissues by deleting Prx III, and in the adrenal gland by deleting Srx or by exposing mice to immobilized stress, I-Prx V accumulates transiently and mature S-Prx V levels decrease in mitochondria over time. These findings support the view that MIP is inhibited by H2O2, resulting in the accumulation and subsequent degradation of I-Prx V, identifying a role for redox mediated regulation of Prx V proteolytic maturation and expression in mitochondria.

scholarly journals Glycine-rich Region of Mitochondrial Processing Peptidase α-Subunit Is Essential for Binding and Cleavage of the Precursor Proteins

2000 ◽  
Vol 275 (44) ◽  
pp. 34552-34556 ◽  
Author(s):  
Yumiko Nagao ◽  
Sakae Kitada ◽  
Katsuhiko Kojima ◽  
Hidehiro Toh ◽  
Satoru Kuhara ◽  
...  
Keyword(s):  
Rich Region ◽  
Α Subunit ◽  
Mitochondrial Processing Peptidase ◽  
Precursor Proteins ◽  
Processing Peptidase

scholarly journals Sequential Processing of a Mitochondrial Tandem Protein: Insights into Protein Import in Schizosaccharomyces pombe

2006 ◽  
Vol 5 (7) ◽  
pp. 997-1006 ◽  
Author(s):  
Oleh Khalimonchuk ◽  
Martin Ott ◽  
Soledad Funes ◽  
Kai Ostermann ◽  
Gerhard Rödel ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Protein Import ◽  
Sequential Processing ◽  
Mitochondrial Processing Peptidase ◽  
Mitochondrial Ribosome ◽  
Genes Encoding ◽  
Processing Site ◽  
Processing Peptidase ◽  
Internal Processing

ABSTRACT The sequencing of the genome of Schizosaccharomyces pombe revealed the presence of a number of genes encoding tandem proteins, some of which are mitochondrial components. One of these proteins (pre-Rsm22-Cox11) consists of a fusion of Rsm22, a component of the mitochondrial ribosome, and Cox11, a factor required for copper insertion into cytochrome oxidase. Since in Saccharomyces cerevisiae, Cox11 is physically attached to the mitochondrial ribosome, it was suggested that the tandem organization of Rsm22-Cox11 is used to covalently tie the mitochondrial ribosome to Cox11 in S. pombe. We report here that pre-Rsm22-Cox11 is matured in two subsequent processing events. First, the mitochondrial presequence is removed. At a later stage of the import process, the Rsm22 and Cox11 domains are separated by cleavage of the mitochondrial processing peptidase at an internal processing site. In vivo data obtained using a tagged version of pre-Rsm22-Cox11 confirmed the proteolytic separation of Cox11 from the Rsm22 domain. Hence, the tandem organization of pre-Rsm22-Cox11 does not give rise to a persistent fusion protein but rather might be used to increase the import efficiency of Cox11 and/or to coordinate expression levels of Rsm22 and Cox11 in S. pombe.

scholarly journals Structural requirement for recognition of the precursor proteins by the mitochondrial processing peptidase.

1994 ◽  
Vol 269 (40) ◽  
pp. 24673-24678
Author(s):  
W.J. Ou ◽  
T. Kumamoto ◽  
K. Mihara ◽  
S. Kitada ◽  
T. Niidome ◽  
...  
Keyword(s):  
Structural Requirement ◽  
Mitochondrial Processing Peptidase ◽  
Precursor Proteins ◽  
Processing Peptidase
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