2006 Fiscal Year Final Research Report Summary
Structures and functions of protein translocator systems
| Project/Area Number |
14037225
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Nagoya University |
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Principal Investigator |
ENDO Toshiya Nagoya University, Grad. Sch. Science, Professor (70152014)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIHISA Tohru Nagoya Univ., RCMS, Associate Professor (60212312)
NISHIKAWA Shuh-ichi Nagoya Univ., Grad, Sch, Science, Associate Prof. (10252222)
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| Project Period (FY) |
2002 – 2006
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| Keywords | mitochnodria / translocator / protein translocation / chaperone / unfolding |
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| Research Abstract |
The central process in the maintenance of functional integrity of mitochondria is the transport of 500-1000 different mitochondrial precursor proteins to mitochondria. Since mitochondria consist of four compartments, the outer and inner membranes, intermembrane space, and matrix, the flux of mitochondrial proteins from the cytosol should branch off in four different sub-fluxes that are directed for each of the four compartments. In the present study, we aimed at elucidation of the mechanisms for surveillance and control of the mitochondrial protein fluxes in yeast cells. We identified 5 new components, Tom38, Toml3, Tim4O, Timl5, and Tim4l, of the mitochondrial protein translocators. Besides, we determined the NMR structure of Timl5, and found that the ability of Tim15 to maintain solubility of mitochondrial Hsp70 represents one of the essential functions of Tim15 in yeast cell growth.
Mitochondrial proteins have to become unfolded to move through the translocator channels. Here we found that the translocation channel of the translocator (Tom40) itself has a chaperone-like activity, thereby promoting unfolding of the substrate proteins to be threaded into the narrow translocator channel. We also analyzed the effects of various stabilization/destabilization mutations in the immunoglobulin-like module of the muscle protein titin on its import from the N-terminus or C-terminus into mitochondria. The effects of mutations on the import of the titin module from the N-terminus correlate well with those on forced mechanical unfolding in atomic force microscopy (AFM) measurements. On the other hand, import of the titin module from the N-terminus is sensitive to mutations in the N-terminal region, but not the ones in the C-terminal region that affect resistance to global unfolding in AFM experiments. We propose that the mitochondrial import system can catalyze precursor unfolding by reducing the stability of unfolding intermediates.
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