Structural and functional association of Trypanosoma brucei MIX protein with cytochrome c oxidase complex.
A mitochondrial inner membrane protein, designated MIX, seems to be essential for cell viability. The deletion of both alleles was not possible, and the deletion of a single allele led to a loss of virulence and aberrant mitochondrial segregation and cell division in Leishmania major. However, the mechanism by which MIX exerts its effect has not been determined. We show here that MIX is also expressed in the mitochondrion of Trypanosoma brucei, and using RNA interference, we found that its loss leads to a phenotype that is similar to that described for Leishmania. The loss of MIX also had a major effect on cytochrome c oxidase activity, on the mitochondrial membrane potential, and on the production of mitochondrial ATP by oxidative phosphorylation. Using a tandem affinity purification tag, we found that MIX is associated with a multiprotein complex that contains subunits of the mitochondrial cytochrome c oxidase complex (respiratory complex IV), the composition of which was characterized in detail. The specific function of MIX is unknown, but it appears to be important for the function of complex IV and for mitochondrial segregation and cell division in T. brucei.
Zíková
Alena
A
Seattle Biomedical Research Institute, 307 Westlake Ave. North, Suite 500, Seattle, WA 98109-5219, USA.
Panigrahi
Aswini K
AK
Uboldi
Alessandro D
AD
Dalley
Rachel A
RA
Handman
Emanuela
E
Stuart
Kenneth
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D053078:Membrane Potential, Mitochondrial; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV
Int J Parasitol. 2001 Nov;31(13):1403-15
11595226
Curr Opin Microbiol. 2007 Dec;10(6):520-7
18023244
Parasitol Res. 2005 Jun;96(3):178-83
15864649
EMBO J. 2001 Jan 15;20(1-2):262-71
11226176
EMBO Rep. 2007 Jun;8(6):589-95
17510656
Mol Biochem Parasitol. 2006 Sep;149(1):65-73
16730807
Eukaryot Cell. 2006 Sep;5(9):1539-49
16963636
J Cell Sci. 2005 Jan 15;118(Pt 2):283-90
15654017
J Biol Chem. 2002 Sep 6;277(36):32849-54
12095995
J Biol Chem. 2006 Sep 1;281(35):25270-7
16825195
Mol Biochem Parasitol. 2007 Jan;151(1):28-40
17097160
Nat Biotechnol. 1999 Oct;17(10):1030-2
10504710
Mol Biochem Parasitol. 1996 Jul;79(1):47-59
8844671
J Biol Chem. 2000 Jun 2;275(22):17160-5
10748081
RNA. 2003 Apr;9(4):484-92
12649499
Methods. 2001 Jul;24(3):218-29
11403571
Trends Parasitol. 2005 Apr;21(4):185-91
15780841
J Biol Chem. 2000 Dec 22;275(51):40174-9
11013266
Mol Biochem Parasitol. 1999 Mar 15;99(1):89-101
10215027
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13207-12
14576278
Mol Microbiol. 2005 Oct;58(1):116-30
16164553
Mol Biol Cell. 2005 Nov;16(11):5410-7
16135527
Nature. 2002 Jan 10;415(6868):141-7
11805826
Int J Parasitol. 2006 Dec;36(14):1499-514
17011565
Mol Biochem Parasitol. 2000 Nov;111(1):87-94
11087919
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1152-7
11792845
J Biol Chem. 2004 Nov 12;279(46):47464-72
15355998
FEBS Lett. 1996 Feb 26;381(1-2):123-6
8641419
Nucleic Acids Res. 2006;34(18):5312-24
17012283
J Bioenerg Biomembr. 1994 Apr;26(2):179-91
8056785
Mol Cell Biol. 2001 Oct;21(20):6833-40
11564867
Mol Cell Proteomics. 2008 Mar;7(3):534-45
18073385
Anal Chem. 2003 Sep 1;75(17):4646-58
14632076
Trends Parasitol. 2005 Aug;21(8):363-9
15967722
Trends Biochem Sci. 2005 Feb;30(2):97-105
15691655
Mol Biochem Parasitol. 2002 Nov-Dec;125(1-2):113-25
12467979
J Biol Chem. 2006 Apr 7;281(14):9677-87
16436376
Mol Cell. 2003 Aug;12(2):307-19
14536071
Mol Cell Proteomics. 2008 Jul;7(7):1286-96
18364347
Curr Genet. 2000 Apr;37(4):234-41
10803885
OMICS. 2002;6(2):207-12
12143966
J Biol Chem. 1989 Oct 25;264(30):17770-6
2808350