title: An Advanced System of the Mitochondrial Processing Peptidase and Core Protein Family in Trypanosoma brucei and Multiple Origins of the Core I Subunit in Eukaryotes.
abstract: Mitochondrial processing peptidase (MPP) consists of α and β subunits that catalyze the cleavage of N-terminal mitochondrial-targeting sequences (N-MTSs) and deliver preproteins to the mitochondria. In plants, both MPP subunits are associated with the respiratory complex bc1, which has been proposed to represent an ancestral form. Subsequent duplication of MPP subunits resulted in separate sets of genes encoding soluble MPP in the matrix and core proteins (cp1 and cp2) of the membrane-embedded bc1 complex. As only α-MPP was duplicated in Neurospora, its single β-MPP functions in both MPP and bc1 complexes. Herein, we investigated the MPP/core protein family and N-MTSs in the kinetoplastid Trypanosoma brucei, which is often considered one of the most ancient eukaryotes. Analysis of N-MTSs predicted in 336 mitochondrial proteins showed that trypanosomal N-MTSs were comparable with N-MTSs from other organisms. N-MTS cleavage is mediated by a standard heterodimeric MPP, which is present in the matrix of procyclic and bloodstream trypanosomes, and its expression is essential for the parasite. Distinct Genes encode cp1 and cp2, and in the bloodstream forms the expression of cp1 is downregulated along with the bc1 complex. Phylogenetic analysis revealed that all eukaryotic lineages include members with a Neurospora-type MPP/core protein family, whereas cp1 evolved independently in metazoans, some fungi and kinetoplastids. Evolution of cp1 allowed the independent regulation of respiration and protein import, which is essential for the procyclic and bloodstream forms of T. brucei. These results indicate that T. brucei possesses a highly derived MPP/core protein family that likely evolved in response to its complex life cycle and does not appear to have an ancient character proposed earlier for this eukaryote.
authors.affiliation: Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Mach
authors.forename: Pavel
authors.initials: P
authors.lastname: Poliak
authors.forename: Anna
authors.initials: A
authors.lastname: Matusková
authors.forename: Vojtĕch
authors.initials: V
authors.lastname: Zárský
authors.forename: Jirí
authors.initials: J
authors.lastname: Janata
authors.forename: Julius
authors.initials: J
authors.lastname: Lukes
authors.forename: Jan
authors.initials: J
authors.lastname: Tachezy
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D008666:Metalloendopeptidases / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D014346:Trypanosoma brucei brucei / Q000235:genetics*; D000096122:Mitochondrial Processing Peptidase
chemical_list: D008666:Metalloendopeptidases; D024101:Mitochondrial Proteins; D000096122:Mitochondrial Processing Peptidase
keywords: bc1 complex; evolution; mitochondrial processing peptidase; mitochondrial targeting sequence; trypanosome
references.citation: J Biochem. 1998 Nov;124(5):1045-9
references.pmid: 9792932
references.citation: Mol Biochem Parasitol. 1999 Mar 15;99(1):89-101
references.pmid: 10215027
references.citation: J Eukaryot Microbiol. 1995 Sep-Oct;42(5):467-72
references.pmid: 7581322
references.citation: Trends Biochem Sci. 1995 May;20(5):171-5
references.pmid: 7610476
references.citation: J Biol Chem. 2000 Nov 3;275(44):34552-6
references.pmid: 10942759
references.citation: J Eukaryot Microbiol. 2012 Sep;59(5):429-93
references.pmid: 23020233
references.citation: Microbiol Rev. 1995 Sep;59(3):325-44
references.pmid: 7565409
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13468-73
references.pmid: 18768799
references.citation: Eukaryot Cell. 2009 Jan;8(1):47-55
references.pmid: 19011120
references.citation: Mol Cell Proteomics. 2011 Sep;10(9):M110.006908
references.pmid: 21610103
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15916-20
references.pmid: 17043242
references.citation: J Cell Sci. 1996 Feb;109 ( Pt 2):517-23
references.pmid: 8838675
references.citation: J Mol Biol. 2010 Mar 12;396(5):1197-210
references.pmid: 20053354
references.citation: J Mol Biol. 1998 Jul 10;280(2):193-9
references.pmid: 9654444
references.citation: J Biol Chem. 2006 Sep 29;281(39):28679-86
references.pmid: 16882667
references.citation: Cell. 2009 Oct 16;139(2):428-39
references.pmid: 19837041
references.citation: Nucleic Acids Res. 2010 Apr;38(7):2145-53
references.pmid: 20047958
references.citation: Ann Trop Med Parasitol. 1984 Jun;78(3):327-30
references.pmid: 6486939
references.citation: Mol Biochem Parasitol. 2012 Oct;185(2):161-4
references.pmid: 22841752
references.citation: Trends Parasitol. 2005 Apr;21(4):185-91
references.pmid: 15780841
references.citation: Int J Parasitol. 2007 Mar;37(3-4):265-72
references.pmid: 17250838
references.citation: Nature. 2006 Mar 30;440(7084):623-30
references.pmid: 16572163
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10426-31
references.pmid: 22699510
references.citation: J Biol Chem. 2001 Mar 2;276(9):6499-505
references.pmid: 11073949
references.citation: J Bioenerg Biomembr. 1999 Jun;31(3):259-74
references.pmid: 10591532
references.citation: Protein Eng. 1990 Oct;4(1):33-7
references.pmid: 2290832
references.citation: Science. 1995 May 26;268(5214):1179-83
references.pmid: 7761835
references.citation: BMC Evol Biol. 2010 Jul 13;10:210
references.pmid: 20626897
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6247-51
references.pmid: 8327505
references.citation: Parasitol Today. 1996 Dec;12(12):465-71
references.pmid: 15275265
references.citation: PLoS Pathog. 2008 Dec;4(12):e1000243
references.pmid: 19096520
references.citation: Eur J Biochem. 2004 Mar;271(6):1209-18
references.pmid: 15009199
references.citation: Mol Biochem Parasitol. 2002 Nov-Dec;125(1-2):211-6
references.pmid: 12467990
references.citation: Nature. 1989 May 11;339(6220):147-9
references.pmid: 2524007
references.citation: J Bioenerg Biomembr. 1996 Jun;28(3):285-92
references.pmid: 8807403
references.citation: Trends Biochem Sci. 1999 Jan;24(1):34-6
references.pmid: 10087920
references.citation: J Biochem. 1994 Jan;115(1):98-107
references.pmid: 8188644
references.citation: Biol Lett. 2010 Jun 23;6(3):342-5
references.pmid: 20031978
references.citation: J Biol Chem. 2009 Oct 30;284(44):30200-8
references.pmid: 19720832
references.citation: Eur J Cell Biol. 1997 Jul;73(3):240-51
references.pmid: 9243185
references.citation: Bioinformatics. 2001 Aug;17(8):754-5
references.pmid: 11524383
references.citation: Trends Cell Biol. 1996 Feb;6(2):56-61
references.pmid: 15157495
references.citation: Cell. 2009 Aug 21;138(4):628-44
references.pmid: 19703392
references.citation: Curr Biol. 2011 Oct 25;21(20):1738-43
references.pmid: 22000100
references.citation: Trends Cell Biol. 2000 Jan;10(1):25-31
references.pmid: 10603473
references.citation: Plant Physiol. 2009 Jul;150(3):1272-85
references.pmid: 19474214
references.citation: J Biochem. 1995 Jun;117(6):1148-50
references.pmid: 7490252
references.citation: Int J Biochem Cell Biol. 1997 Aug-Sep;29(8-9):1043-5
references.pmid: 9415998
references.citation: Mol Biol Evol. 2009 Sep;26(9):1941-7
references.pmid: 19531743
references.citation: J Biochem. 1997 Nov;122(5):1019-23
references.pmid: 9443819
references.citation: Biosci Biotechnol Biochem. 2008 Jul;72(7):1836-46
references.pmid: 18603769
references.citation: Arch Biochem Biophys. 1996 Nov 1;335(1):211-8
references.pmid: 8914853
references.citation: PLoS One. 2011;6(9):e24428
references.pmid: 21935410
references.citation: Mol Biol Evol. 2009 Mar;26(3):671-80
references.pmid: 19091722
references.citation: Eur J Biochem. 1991 Jul 1;199(1):123-31
references.pmid: 1712295
references.citation: Mol Microbiol. 2008 Jul;69(1):94-109
references.pmid: 18433447
references.citation: Mol Biochem Parasitol. 2000 Mar 5;106(2):249-60
references.pmid: 10699254
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: J Mol Biol. 2011 Mar 18;407(1):180-92
references.pmid: 21262231
references.citation: Trends Cell Biol. 2008 Jan;18(1):12-8
references.pmid: 18068984
references.citation: FEBS J. 2008 May;275(10):2385-402
references.pmid: 18393999
references.citation: Bioinformatics. 2005 Dec 15;21(24):4338-47
references.pmid: 16234323
references.citation: J Mol Evol. 2012 Oct;75(3-4):119-29
references.pmid: 23064754
references.citation: Structure. 2001 Jul 3;9(7):615-25
references.pmid: 11470436
references.citation: J Biochem. 1999 Nov;126(5):874-8
references.pmid: 10544280
references.citation: J Bacteriol. 2007 Feb;189(3):844-50
references.pmid: 17158683
references.citation: Biochim Biophys Acta. 1995 Nov 30;1269(3):201-4
references.pmid: 7495871
references.citation: J Biol Chem. 1990 Jun 15;265(17):9881-7
references.pmid: 2141023
references.citation: Cell. 2002 Feb 22;108(4):435-8
references.pmid: 11909515
references.citation: Biochim Biophys Acta. 2013 Feb;1833(2):360-70
references.pmid: 22495024
references.citation: Trends Parasitol. 2008 Jul;24(7):310-7
references.pmid: 18534909
references.citation: Proteomics. 2009 Jan;9(2):434-50
references.pmid: 19105172
references.citation: Biochim Biophys Acta. 2002 Sep 2;1592(1):63-77
references.pmid: 12191769
references.citation: Curr Biol. 2012 Jun 19;22(12):R479-81; author reply R481-2
references.pmid: 22720677
references.citation: Ann N Y Acad Sci. 1987;503:17-54
references.pmid: 3113314
references.citation: Biochem Biophys Res Commun. 2004 Mar 26;316(1):211-7
references.pmid: 15003532
references.citation: Eukaryot Cell. 2010 Nov;9(11):1702-10
references.pmid: 20833891
references.citation: Annu Rev Biochem. 2007;76:723-49
references.pmid: 17263664
references.citation: Proteins. 1998 Jan;30(1):49-60
references.pmid: 9443340