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Updated: Jul 14, 2026

Analysis of the Expression and Complexes Assembly of the Mitochondrial Respiratory Chain Proteins in the Fission Yeast Schizosaccharomyces pombe
Published on: May 2, 2025
Structural basis of functional cooperation of Tim15/Zim17 with yeast mitochondrial Hsp70
Takaki Momose1, Chié Ohshima, Masahiro Maeda
1Department of Chemistry, Graduate School of Science, Nagoya University, Japan.
Abstract:
Mitochondrial heat-shock protein 70 (mtHsp70) and its partner proteins drive protein import into the matrix. Tim15/Zim17/Hep1 is a mtHsp70 partner protein on the matrix side of the inner mitochondrial membrane. We determined the nuclear magnetic resonance (NMR) structure of the core domain of Tim15. On the basis of the NMR structure, we created Tim15 mutants and tested their ability to complement the functional defects of Tim15 depletion and to suppress self-aggregation of mtHsp70 in vivo. A pair of basic residues, Arg 106 and His 107, conserved Asp 111 and flexible loop 133-137, and were important (Arg 106-His 107 pair and Asp 111) or partly important (the loop 133-137) for yeast cell growth, mitochondrial protein import and the suppression of mtHsp70 aggregation. Therefore, the function of Tim15 in yeast cell growth is well correlated with its ability to suppress mtHsp70 aggregation, although it is still unknown whether inhibition of mtHsp70 aggregation is the primary function of Tim15.
Insights
Mitochondrial heat-shock protein 70 (mtHsp70) partner Tim15
Area of Science:
- Mitochondrial biology
- Protein homeostasis
- Structural biology
Background:
- Mitochondrial heat-shock protein 70 (mtHsp70) and its partners facilitate protein import into the mitochondrial matrix.
- Tim15 (also known as Zim17/Hep1) is a crucial mtHsp70 partner protein located on the matrix side of the inner mitochondrial membrane.
- Understanding Tim15's structure and function is key to elucidating mitochondrial protein import mechanisms.
Purpose of the Study:
- To determine the nuclear magnetic resonance (NMR) structure of the Tim15 core domain.
- To investigate the role of specific Tim15 residues and structural features in yeast cell growth, mitochondrial protein import, and mtHsp70 aggregation.
- To correlate Tim15's function in cell growth with its ability to suppress mtHsp70 aggregation.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy to determine the 3D structure of the Tim15 core domain.
- Site-directed mutagenesis to create Tim15 variants.
- Functional assays in yeast to assess cell growth, mitochondrial protein import efficiency, and mtHsp70 aggregation suppression.
Main Results:
- The NMR structure of the Tim15 core domain was determined.
- A pair of basic residues (Arg 106 and His 107), conserved Asp 111, and a flexible loop (residues 133-137) were identified as important for Tim15 function.
- These specific regions were found to be critical for yeast cell growth, mitochondrial protein import, and suppression of mtHsp70 aggregation in vivo.
Conclusions:
- The study elucidated the structure of the Tim15 core domain, revealing key functional regions.
- Specific residues and structural elements within Tim15 are essential for maintaining yeast cell viability and mitochondrial protein import.
- Tim15's role in suppressing mtHsp70 aggregation is strongly linked to its function in cell growth, though its primary role remains under investigation.
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