Unique Interactions of the Small Translocases of the Mitochondrial Inner Membrane (Tims) in Trypanosoma brucei .

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Trypanosoma brucei brucei*/metabolism; Mitochondrial Membranes/metabolism ; Membrane Transport Proteins/analysis ; Saccharomyces cerevisiae/metabolism ; Protozoan Proteins/chemistry

The infectious agent for African trypanosomiasis, Trypanosoma brucei , possesses a unique and essential translocase of the mitochondrial inner membrane, known as the TbTIM17 complex. TbTim17 associates with six small TbTims (TbTim9, TbTim10, TbTim11, TbTim12, TbTim13, and TbTim8/13). However, the interaction patterns of these smaller TbTims with each other and TbTim17 are not clear. Through yeast two-hybrid (Y2H) and co-immunoprecipitation analyses, we demonstrate that all six small TbTims interact with each other. Stronger interactions were found among TbTim8/13, TbTim9, and TbTim10. However, TbTim10 shows weaker associations with TbTim13, which has a stronger connection with TbTim17. Each of the small TbTims also interacts strongly with the C-terminal region of TbTim17. RNAi studies indicated that among all small TbTims, TbTim13 is most crucial for maintaining the steady-state levels of the TbTIM17 complex. Further analysis of the small TbTim complexes by size exclusion chromatography revealed that each small TbTim, except for TbTim13, is present in ~70 kDa complexes, possibly existing in heterohexameric forms. In contrast, TbTim13 is primarily present in the larger complex (>800 kDa) and co-fractionates with TbTim17. Altogether, our results demonstrate that, relative to other eukaryotes, the architecture and function of the small TbTim complexes are specific to T. brucei .

Update of: bioRxiv. 2023 May 31;:. (PMID: 37398442)

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R01 AI125662 United States AI NIAID NIH HHS; U54 CA163069 United States CA NCI NIH HHS; G12 MD007586 United States MD NIMHD NIH HHS; S10 RR025497 United States RR NCRR NIH HHS; U54 MD007586 United States MD NIMHD NIH HHS; 2R25GM059994 United States GM NIGMS NIH HHS; R25 GM059994 United States GM NIGMS NIH HHS; MD007586, CA163069, and S10RR025497 United States GM NIGMS NIH HHS

Keywords: Trypanosoma brucei; mitochondria; protein interactions; small Tims; translocase

0 (Membrane Transport Proteins)
0 (Protozoan Proteins)

Date Created: 20240210 Date Completed: 20240214 Latest Revision: 20240219

20240219

PMC10855554

10.3390/ijms25031415

38338692