title: Mitochondrial biogenesis, switching the sorting pathway of the intermembrane space receptor Mia40.
abstract: Mitochondrial precursor proteins are directed into the intermembrane space via two different routes, the presequence pathway and the redox-dependent MIA pathway. The pathways were assumed to be independent and transport different proteins. We report that the intermembrane space receptor Mia40 can switch between both pathways. In fungi, Mia40 is synthesized as large protein with an N-terminal presequence, whereas in metazoans and plants, Mia40 consists only of the conserved C-terminal domain. Human MIA40 and the C-terminal domain of yeast Mia40 (termed Mia40(core)) rescued the viability of Mia40-deficient yeast independently of the presence of a presequence. Purified Mia40(core) was imported into mitochondria via the MIA pathway. With cells expressing both full-length Mia40 and Mia40(core), we demonstrate that yeast Mia40 contains dual targeting information, directing the large precursor onto the presequence pathway and the smaller Mia40(core) onto the MIA pathway, raising interesting implications for the evolution of mitochondrial protein sorting.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.forename: Agnes
authors.initials: A
authors.lastname: Schulze-Specking
authors.forename: Kipros
authors.initials: K
authors.lastname: Gabriel
authors.forename: Stephan
authors.initials: S
authors.lastname: Kutik
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
mesh_terms: D000818:Animals; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D008954:Models, Biological; D010084:Oxidation-Reduction; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D013696:Temperature
chemical_list: C507282:CHCHD4 protein, human; C495320:MIA40 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins
references.citation: J Mol Biol. 2000 Jul 21;300(4):1005-16
references.pmid: 10891285
references.citation: Nat Struct Biol. 2001 Dec;8(12):1008-10
references.pmid: 11723465
references.citation: J Mol Biol. 2007 Jan 19;365(3):612-20
references.pmid: 17095012
references.citation: Proteomics. 2004 Jun;4(6):1581-90
references.pmid: 15174128
references.citation: Eur J Biochem. 2003 Apr;270(7):1528-35
references.pmid: 12654008
references.citation: EMBO J. 2004 Oct 1;23(19):3735-46
references.pmid: 15359280
references.citation: J Mol Biol. 2005 Nov 11;353(5):937-44
references.pmid: 16185707
references.citation: FEBS Lett. 2005 Jan 3;579(1):179-84
references.pmid: 15620710
references.citation: FEBS Lett. 2007 Mar 20;581(6):1098-102
references.pmid: 17336303
references.citation: J Biol Chem. 2007 Aug 3;282(31):22472-80
references.pmid: 17553782
references.citation: Annu Rev Biochem. 2007;76:723-49
references.pmid: 17263664
references.citation: Mol Microbiol. 2007 Sep;65(5):1360-73
references.pmid: 17680986
references.citation: Cell. 2005 Mar 25;120(6):817-29
references.pmid: 15797382
references.citation: J Mol Biol. 2005 Oct 28;353(3):517-28
references.pmid: 16185709
references.citation: Science. 2006 Jul 21;313(5785):314-8
references.pmid: 16857931
references.citation: Nat Cell Biol. 2007 Oct;9(10):1152-9
references.pmid: 17828250
references.citation: Cell. 2005 Jul 1;121(7):1059-69
references.pmid: 15989955
references.citation: J Biol Chem. 2004 Nov 12;279(46):47815-21
references.pmid: 15364952
references.citation: Cell. 2005 Jul 1;121(7):965-7
references.pmid: 15989945
references.citation: Cell. 1992 May 29;69(5):809-22
references.pmid: 1350514
references.citation: Trends Biochem Sci. 2004 Jan;29(1):1-4
references.pmid: 14729324
references.citation: J Mol Biol. 2005 Oct 28;353(3):485-92
references.pmid: 16181637
references.citation: J Biol Chem. 2007 Dec 28;282(52):37461-70
references.pmid: 17959605
references.citation: J Cell Sci. 2003 Aug 15;116(Pt 16):3259-67
references.pmid: 12857785
references.citation: Biochim Biophys Acta. 2008 Apr;1783(4):610-7
references.pmid: 17996737
references.citation: Mol Biol Cell. 2008 Jan;19(1):226-36
references.pmid: 17978092
references.citation: Mol Cell. 2005 Apr 15;18(2):145-6
references.pmid: 15837417
references.citation: Curr Biol. 2003 Apr 15;13(8):R326-37
references.pmid: 12699647
references.citation: Comput Appl Biosci. 1996 Aug;12(4):357-8
references.pmid: 8902363
references.citation: Eur J Biochem. 1996 Nov 1;241(3):779-86
references.pmid: 8944766