Novel IM-associated protein Tim54 plays a role in the mitochondrial import of internal signal-containing proteins in Trypanosoma brucei.
Mitochondrial
TbTim17
TbTim54
Translocase
Trypanosoma brucei
Journal
Biology of the cell
ISSN: 1768-322X
Titre abrégé: Biol Cell
Pays: England
ID NLM: 8108529
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
18
04
2020
accepted:
28
08
2020
pubmed:
22
10
2020
medline:
31
8
2021
entrez:
21
10
2020
Statut:
ppublish
Résumé
The translocase of the mitochondrial inner membrane (TIM) imports most of the nucleus-encoded proteins that are destined for the matrix, inner membrane (IM) and the intermembrane space (IMS). Trypanosoma brucei, the infectious agent for African trypanosomiasis, possesses a unique TIM complex consisting of several novel proteins in association with a relatively conserved protein TbTim17. Tandem affinity purification of the TbTim17 protein complex revealed TbTim54 as a potential component of this complex. TbTim54, a trypanosome-specific IMS protein, is peripherally associated with the IM and is present in a protein complex slightly larger than the TbTim17 complex. TbTim54 knockdown (KD) reduced the import of TbTim17 and compromised the integrity of the TbTim17 complex. TbTim54 KD inhibited the in vitro mitochondrial import and assembly of the internal signal-containing mitochondrial carrier proteins MCP3, MCP5 and MCP11 to a greater extent than TbTim17 KD. Furthermore, TbTim54 KD, but not TbTim17 KD, significantly hampered the mitochondrial targeting of ectopically expressed MCP3 and MCP11. These observations along with our previous finding that the mitochondrial import of N-terminal signal-containing proteins like cytochrome oxidase subunit 4 and MRP2 was affected to a greater extent by TbTim17 KD than TbTim54 KD indicating a substrate-specificity of TbTim54 for internal-signal containing mitochondrial proteins. In other organisms, small Tim chaperones in the IMS are known to participate in the translocation of MCPs. We found that TbTim54 can directly interact with at least two of the six known small TbTim proteins, TbTim11 and TbTim13, as well as with the N-terminal domain of TbTim17. TbTim54 interacts with TbTim17. It also plays a crucial role in the mitochondrial import and complex assembly of internal signal-containing IM proteins in T. brucei. We are the first to characterise TbTim54, a novel TbTim that is involved primarily in the mitochondrial import of MCPs and TbTim17 in T. brucei.
Sections du résumé
BACKGROUND
BACKGROUND
The translocase of the mitochondrial inner membrane (TIM) imports most of the nucleus-encoded proteins that are destined for the matrix, inner membrane (IM) and the intermembrane space (IMS). Trypanosoma brucei, the infectious agent for African trypanosomiasis, possesses a unique TIM complex consisting of several novel proteins in association with a relatively conserved protein TbTim17. Tandem affinity purification of the TbTim17 protein complex revealed TbTim54 as a potential component of this complex.
RESULTS
RESULTS
TbTim54, a trypanosome-specific IMS protein, is peripherally associated with the IM and is present in a protein complex slightly larger than the TbTim17 complex. TbTim54 knockdown (KD) reduced the import of TbTim17 and compromised the integrity of the TbTim17 complex. TbTim54 KD inhibited the in vitro mitochondrial import and assembly of the internal signal-containing mitochondrial carrier proteins MCP3, MCP5 and MCP11 to a greater extent than TbTim17 KD. Furthermore, TbTim54 KD, but not TbTim17 KD, significantly hampered the mitochondrial targeting of ectopically expressed MCP3 and MCP11. These observations along with our previous finding that the mitochondrial import of N-terminal signal-containing proteins like cytochrome oxidase subunit 4 and MRP2 was affected to a greater extent by TbTim17 KD than TbTim54 KD indicating a substrate-specificity of TbTim54 for internal-signal containing mitochondrial proteins. In other organisms, small Tim chaperones in the IMS are known to participate in the translocation of MCPs. We found that TbTim54 can directly interact with at least two of the six known small TbTim proteins, TbTim11 and TbTim13, as well as with the N-terminal domain of TbTim17.
CONCLUSION
CONCLUSIONS
TbTim54 interacts with TbTim17. It also plays a crucial role in the mitochondrial import and complex assembly of internal signal-containing IM proteins in T. brucei.
SIGNIFICANCE
CONCLUSIONS
We are the first to characterise TbTim54, a novel TbTim that is involved primarily in the mitochondrial import of MCPs and TbTim17 in T. brucei.
Identifiants
pubmed: 33084070
doi: 10.1111/boc.202000054
pmc: PMC8265390
mid: NIHMS1720309
doi:
Substances chimiques
Membrane Transport Proteins
0
Mitochondrial Proteins
0
Protozoan Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
39-57Subventions
Organisme : NIAID NIH HHS
ID : R01 AI125662
Pays : United States
Organisme : NIGMS NIH HHS
ID : 2SC1GM081146
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : 1RO1AI125662
Organisme : NIMHD NIH HHS
ID : S21 MD000104
Pays : United States
Organisme : National Science Foundation
ID : U54RR026140/U54MD007593
Organisme : NIAID NIH HHS
ID : T32 AI007281
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007593
Pays : United States
Organisme : NIGMS NIH HHS
ID : SC1 GM081146
Pays : United States
Organisme : NCRR NIH HHS
ID : U54 RR026140
Pays : United States
Informations de copyright
© 2020 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.
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