Article ; Online: Molecular pathway of mitochondrial preprotein import through the TOM-TIM23 supercomplex.
Nature structural & molecular biology
2023 Volume 30, Issue 12, Page(s) 1996–2008
Abstract: ... controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane ... The mechanisms through which proteins are translocated via the TOM and TIM23 complexes remain unclear. Here ... we report the assembly of the active TOM-TIM23 supercomplex of Saccharomyces cerevisiae with translocating ...
Abstract | Over half of mitochondrial proteins are imported from the cytosol via the pre-sequence pathway, controlled by the TOM complex in the outer membrane and the TIM23 complex in the inner membrane. The mechanisms through which proteins are translocated via the TOM and TIM23 complexes remain unclear. Here we report the assembly of the active TOM-TIM23 supercomplex of Saccharomyces cerevisiae with translocating polypeptide substrates. Electron cryo-microscopy analyses reveal that the polypeptide substrates pass the TOM complex through the center of a Tom40 subunit, interacting with a glutamine-rich region. Structural and biochemical analyses show that the TIM23 complex contains a heterotrimer of the subunits Tim23, Tim17 and Mgr2. The polypeptide substrates are shielded from lipids by Mgr2 and Tim17, which creates a translocation pathway characterized by a negatively charged entrance and a central hydrophobic region. These findings reveal an unexpected pre-sequence pathway through the TOM-TIM23 supercomplex spanning the double membranes of mitochondria. |
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MeSH term(s) | Membrane Transport Proteins/chemistry ; Mitochondrial Precursor Protein Import Complex Proteins ; Carrier Proteins/metabolism ; Mitochondrial Membrane Transport Proteins/chemistry ; Saccharomyces cerevisiae Proteins/metabolism ; Protein Transport ; Mitochondria/metabolism ; Saccharomyces cerevisiae/metabolism ; Mitochondrial Proteins/metabolism ; Peptides/metabolism ; Membrane Proteins/metabolism |
Chemical Substances | Membrane Transport Proteins ; Mitochondrial Precursor Protein Import Complex Proteins ; Carrier Proteins ; Mitochondrial Membrane Transport Proteins ; Saccharomyces cerevisiae Proteins ; Mitochondrial Proteins ; Peptides ; TIM23 protein, S cerevisiae ; Mgr2 protein, S cerevisiae ; Membrane Proteins ; Tom40 protein, S cerevisiae |
Language | English |
Publishing date | 2023-09-11 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 2126708-X |
ISSN | 1545-9985 ; 1545-9993 |
ISSN (online) | 1545-9985 |
ISSN | 1545-9993 |
DOI | 10.1038/s41594-023-01103-7 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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