Complexes |
Subunits |
Depletion effects |
Yeast ortholog |
References |
ATOM |
ATOM40 |
Reduction in levels of ATOM14, ATOM11, ATOM46, and ATOM69 |
Tom40 |
52
52. Pusnik M, Schmidt O, Perry AJ, Oeljeklaus S, Niemann M, Warscheid B, et al. Mitochondrial preprotein translocase of trypanosomatids has a bacterial origin. Curr Biol. 2011; 21: 1738-43.
,
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
,
82
82. Harsman A, Niemann M, Pusnik M, Schmidt O, Burmann BM, Hiller S, et al. Bacterial origin of a mitochondrial outer membrane protein translocase: new perspectives from comparative single channel electrophysiology. J Biol Chem. 2012; 287: 31437-45.
,
83
83. Niemann M, Harsman A, Mani J, Peikert CD, Oeljeklaus S, Warscheid B, et al. tRNAs and proteins use the same import channel for translocation across the mitochondrial outer membrane of trypanosomes. Proc Natl Acad Sci USA. 2017; 114: E7679-87.
|
ATOM14 |
Impairment of protein and tRNA import |
Tom22 |
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
,
83
83. Niemann M, Harsman A, Mani J, Peikert CD, Oeljeklaus S, Warscheid B, et al. tRNAs and proteins use the same import channel for translocation across the mitochondrial outer membrane of trypanosomes. Proc Natl Acad Sci USA. 2017; 114: E7679-87.
|
ATOM46 |
not described |
- |
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
|
ATOM69 |
Accumulation of cytosolic precursor proteins; parasite growth arrest |
- |
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
|
ATOM11 |
Inhibition of tRNA import |
- |
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
,
83
83. Niemann M, Harsman A, Mani J, Peikert CD, Oeljeklaus S, Warscheid B, et al. tRNAs and proteins use the same import channel for translocation across the mitochondrial outer membrane of trypanosomes. Proc Natl Acad Sci USA. 2017; 114: E7679-87.
|
ATOM12 |
Inhibition of tRNA import |
- |
53
53. Mani J, Desy S, Niemann M, Chanfon A, Oeljeklaus S, Pusnik M, et al. Mitochondrial protein import receptors in Kinetoplastids reveal convergent evolution over large phylogenetic distances. Nat Commun. 2015; 6: 6646.
|
ATOM19 |
Inhibition of mitochondrial protein import, ΔΨm and kDNA loss, decline in O2 uptake and parasite growth arrest |
- |
84
84. Povelones ML, Tiengwe C, Gluenz E, Gull K, Englund PT, Jensen RE. Mitochondrial shape and function in trypanosomes requires the outer membrane protein, TbLOK1. Mol Microbiol. 2013; 87: 713-29.
,
85
85. Desy S, Mani J, Harsman A, Käser S, Schneider A. TbLOK1/ATOM19 is a novel subunit of the noncanonical mitochondrial outer membrane protein translocase of Trypanosoma brucei. Mol Microbiol. 2016; 102: 520-9.
|
SAM |
Sam50 |
not described |
Sam50 |
56
56. Sharma S, Singha UK, Chaudhuri M. Role of Tob55 on mitochondrial protein biogenesis in Trypanosoma brucei. Mol Biochem Parasitol. 2010; 174: 89-100.
|
Sam35 |
not described |
Sam35 |
57
57. Niemann M, Wiese S, Mani J, Chanfon A, Jackson C, Meisinger C, et al. Mitochondrial outer membrane proteome of Trypanosoma brucei reveals novel factors required to maintain mitochondrial morphology. Mol Cell Proteomics. 2013; 12: 515-28.
|
OTHERS |
pATOM36 |
Alteration in MOM protein composition, kDNA loss and increased distance basal body - MOM |
- |
58
58. Pusnik M, Mani J, Schmidt O, Niemann M, Oeljeklaus S, Schnarwiler F, et al. An essential novel component of the noncanonical mitochondrial outer membrane protein import system of trypanosomatids. Mol Biol Cell. 2012; 23: 3420-8.
,
62
62. Käser S, Oeljeklaus S, Týc J, Vaughan S, Warscheid B, Schneider A. Outer membrane protein functions as integrator of protein import and DNA inheritance in mitochondria. Proc Natl Acad Sci USA. 2016; 113: E4467-75.
|
Erv1 |
Reduction in abundance of small TIMs and cysteine-rich substrates in MIS |
Erv1 |
70
70. Basu S, Leonard JC, Desai N, Mavridou DAI, Tang KH, Goddard AD, et al. Divergence of Erv1-associated mitochondrial import and export pathways in trypanosomes and anaerobic protists. Eukaryot Cell. 2013; 12: 343-55.
,
71
71. Eckers E, Petrungaro C, Gross D, Riemer J, Hell K, Deponte M. Divergent molecular evolution of the mitochondrial sulfhydryl:cytochrome C oxidoreductase Erv in opisthokonts and parasitic protists. J Biol Chem. 2013; 288: 2676-88.
|
TIM |
TbTim17 |
Inhibition of the mitochondrial import of proteins and the newly synthesised tRNA; impairment of the mitochondrial import of cytochrome oxidase subunit IV and decreased ΔΨm |
Tim17/22/23 |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
,
76
76. Tschopp F, Charrière F, Schneider A. In vivo study in Trypanosoma brucei links mitochondrial transfer RNA import to mitochondrial protein import. EMBO Rep. 2011; 12: 825-32.
,
86
86. Singha UK, Peprah E, Williams S, Walker R, Saha L, Chaudhuri M. Characterization of the mitochondrial inner membrane protein translocator Tim17 from Trypanosoma brucei. Mol Biochem Parasitol. 2008; 159: 30-43.
|
TbTim62 |
Inhibition of import of mitochondrial proteins in vitro; reduction in mitochondrial protein content in vivo
|
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
|
ACAD |
not described |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
|
TbTim42 |
not described |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
|
TimRhom I |
Impairment of cytochrome oxidase subunit 4 import |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
87
87. Shikha S, Huot JL, Schneider A, Niemann M. tRNA import across the mitochondrial inner membrane in T. brucei requires TIM subunits but is independent of protein import. Nucleic Acids Res. 2020; 48: 12269-81.
|
TimRhom II |
Impairment of cytochrome oxidase subunit 4 import |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
87
87. Shikha S, Huot JL, Schneider A, Niemann M. tRNA import across the mitochondrial inner membrane in T. brucei requires TIM subunits but is independent of protein import. Nucleic Acids Res. 2020; 48: 12269-81.
|
TbTim50 |
kDNA overreplication, ΔΨm decrease and cell growth in the bloodstream form of T. brucei
|
- |
80
80. Duncan MR, Fullerton M, Chaudhuri M. Tim50 in Trypanosoma brucei possesses a dual specificity phosphatase activity and is critical for mitochondrial protein import. J Biol Chem. 2013; 288: 3184-97.
,
81
81. Tripathi A, Singha UK, Cooley A, Gillyard T, Krystofiak E, Pratap S, et al. Trypanosoma brucei Tim50 possesses PAP activity and plays a critical role in cell cycle regulation and parasite infectivity. MBio. 2021; 12(5): e0159221.
|
TbTim47 |
Inhibit in vitro import of mitochondrial proteins |
- |
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
|
TbTim54 |
Inhibit in vitro import of mitochondrial proteins; impacts negatively the protein content in vivo
|
- |
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
|
PAM |
mHsp70 |
Impairs mitochondrial import of proteins and tRNA |
mHsp70 |
75
75. Singha UK, Hamilton VN, Duncan MR, Weems E, Tripathi MK, Chaudhuri M. Protein translocase of mitochondrial inner membrane in Trypanosoma brucei. J Biol Chem. 2012; 287: 14480-93.
,
76
76. Tschopp F, Charrière F, Schneider A. In vivo study in Trypanosoma brucei links mitochondrial transfer RNA import to mitochondrial protein import. EMBO Rep. 2011; 12: 825-32.
|
Mge1 |
not described |
Mge1 |
88
88. Týč J, Klingbeil MM, Lukeš J. Mitochondrial heat shock protein machinery hsp70/hsp40 is indispensable for proper mitochondrial DNA maintenance and replication. MBio. 2015; 6(1): e02425-14.
|
TbPam16 |
Parasite growth arrest |
- |
79
79. Känel C, Muñoz-Gómez SA, Oeljeklaus S, Wenger C, Warscheid B, Wideman JG. Homologue replacement in the import motor of the mitochondrial inner membrane of trypanosomes. Elife. 2020; 9: e52560.
|
TbPam18 |
Parasite growth arrest |
- |
79
79. Känel C, Muñoz-Gómez SA, Oeljeklaus S, Wenger C, Warscheid B, Wideman JG. Homologue replacement in the import motor of the mitochondrial inner membrane of trypanosomes. Elife. 2020; 9: e52560.
|
TbPam27 |
Parasite growth arrest; and accumulation of cytochrome oxidase subunit 4 |
- |
79
79. Känel C, Muñoz-Gómez SA, Oeljeklaus S, Wenger C, Warscheid B, Wideman JG. Homologue replacement in the import motor of the mitochondrial inner membrane of trypanosomes. Elife. 2020; 9: e52560.
|
Small Tims |
Tim9 |
Parasite growth arrest and reduced levels of TbTim17 |
Tim9 |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
64
64. Gentle IE, Perry AJ, Alcock FH, Likić VA, Dolezal P, Ng ET, et al. Conserved motifs reveal details of ancestry and structure in the small TIM chaperones of the mitochondrial intermembrane space. Mol Biol Evol. 2007; 24: 1149-60.
,
68
68. Smith JT, Singha UK, Misra S, Chaudhuri M. Divergent Small Tim homologues are associated with TbTim17 and critical for the biogenesis of TbTim17 protein complexes in Trypanosoma brucei. mSphere. 2018; 3(3): e00204-18.
|
Tim10 |
Parasite growth arrest and reduced levels of TbTim17 |
Tim10 |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
64
64. Gentle IE, Perry AJ, Alcock FH, Likić VA, Dolezal P, Ng ET, et al. Conserved motifs reveal details of ancestry and structure in the small TIM chaperones of the mitochondrial intermembrane space. Mol Biol Evol. 2007; 24: 1149-60.
,
68
68. Smith JT, Singha UK, Misra S, Chaudhuri M. Divergent Small Tim homologues are associated with TbTim17 and critical for the biogenesis of TbTim17 protein complexes in Trypanosoma brucei. mSphere. 2018; 3(3): e00204-18.
|
Tim8/13 |
Parasite growth arrest and reduced levels of TbTim17 |
Tim8/13 |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
64
64. Gentle IE, Perry AJ, Alcock FH, Likić VA, Dolezal P, Ng ET, et al. Conserved motifs reveal details of ancestry and structure in the small TIM chaperones of the mitochondrial intermembrane space. Mol Biol Evol. 2007; 24: 1149-60.
,
66
66. Eckers E, Cyrklaff M, Simpson L, Deponte M. Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Biol Chem. 2012; 393: 513-24.
,
68
68. Smith JT, Singha UK, Misra S, Chaudhuri M. Divergent Small Tim homologues are associated with TbTim17 and critical for the biogenesis of TbTim17 protein complexes in Trypanosoma brucei. mSphere. 2018; 3(3): e00204-18.
|
Tim11 |
not described |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
66
66. Eckers E, Cyrklaff M, Simpson L, Deponte M. Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Biol Chem. 2012; 393: 513-24.
|
Tim12 |
not described |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
,
66
66. Eckers E, Cyrklaff M, Simpson L, Deponte M. Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries. Biol Chem. 2012; 393: 513-24.
|
Tim13 |
not described |
- |
54
54. Harsman A, Oeljeklaus S, Wenger C, Huot JL, Warscheid B, Schneider A. The non-canonical mitochondrial inner membrane presequence translocase of trypanosomatids contains two essential rhomboid-like proteins. Nat Commun. 2016; 7: 13707.
|