PMID- 33084070
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20230228
IS  - 1768-322X (Electronic)
IS  - 0248-4900 (Print)
IS  - 0248-4900 (Linking)
VI  - 113
IP  - 1
DP  - 2021 Jan
TI  - Novel IM-associated protein Tim54 plays a role in the mitochondrial import of 
      internal signal-containing proteins in Trypanosoma brucei.
PG  - 39-57
LID - 10.1111/boc.202000054 [doi]
AB  - 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: 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: 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: 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.
CI  - (c) 2020 Societe Francaise des Microscopies and Societe de Biologie Cellulaire de 
      France. Published by John Wiley & Sons Ltd.
FAU - Singha, Ujjal K
AU  - Singha UK
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Tripathi, Anuj
AU  - Tripathi A
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Smith, Joseph T Jr
AU  - Smith JT Jr
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Quinones, Linda
AU  - Quinones L
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Saha, Aparajita
AU  - Saha A
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Singha, Tanusree
AU  - Singha T
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
FAU - Chaudhuri, Minu
AU  - Chaudhuri M
AUID- ORCID: 0000-0001-7626-1280
AD  - Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN, 
      37208, USA.
LA  - eng
GR  - R01 AI125662/AI/NIAID NIH HHS/United States
GR  - 2SC1GM081146/GM/NIGMS NIH HHS/United States
GR  - 1RO1AI125662/National Institute of Allergy and Infectious Diseases/
GR  - S21 MD000104/MD/NIMHD NIH HHS/United States
GR  - U54RR026140/U54MD007593/National Science Foundation/
GR  - T32 AI007281/AI/NIAID NIH HHS/United States
GR  - U54 MD007593/MD/NIMHD NIH HHS/United States
GR  - SC1 GM081146/GM/NIGMS NIH HHS/United States
GR  - U54 RR026140/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20201109
PL  - England
TA  - Biol Cell
JT  - Biology of the cell
JID - 8108529
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Protozoan Proteins)
SB  - IM
MH  - Membrane Transport Proteins/*physiology
MH  - Mitochondria/metabolism
MH  - Mitochondrial Membranes/metabolism
MH  - Mitochondrial Proteins/*physiology
MH  - Protein Transport
MH  - Protozoan Proteins/*physiology
MH  - Trypanosoma brucei brucei/*metabolism
PMC - PMC8265390
MID - NIHMS1720309
OTO - NOTNLM
OT  - Mitochondrial
OT  - TbTim17
OT  - TbTim54
OT  - Translocase
OT  - Trypanosoma brucei
COIS- Conflict of Interest: The authors declare that no conflicts of interest exists.
EDAT- 2020/10/22 06:00
MHDA- 2021/08/31 06:00
PMCR- 2021/07/08
CRDT- 2020/10/21 06:07
PHST- 2020/04/18 00:00 [received]
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/10/22 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2020/10/21 06:07 [entrez]
PHST- 2021/07/08 00:00 [pmc-release]
AID - 10.1111/boc.202000054 [doi]
PST - ppublish
SO  - Biol Cell. 2021 Jan;113(1):39-57. doi: 10.1111/boc.202000054. Epub 2020 Nov 9.