A selectivity filter in Tim17 mediates intramitochondrial protein sorting
Abstract
Mitochondria import hundreds of proteins into the matrix and the inner membrane (IM). The translocase of the IM of mitochondria (TIM23 complex) sorts these proteins using topogenic signals in their structure and directs them into the matrix or inserts them into the IM. How these signals are deciphered is unknown. Here we show that Tim17, the protein-conducting subunit of the TIM23 complex, contains a highly conserved selectivity filter for incoming proteins. Using a fluorescence-based sorting reporter, we identified the mitochondrial oxidoreductase Dmo2 (akin to DMAC1 in humans) as factor for intramitochondrial protein sorting. Molecular dynamics simulations show that a Dmo2-dependent disulfide bond into Tim17 constitutes a negatively charged selectivity filter at the vestibule of the TIM23 complex that arrests membrane proteins and facilitates the lateral insertion. Our work provides a molecular rationale as to how the TIM23 translocase differentiates between soluble and membrane proteins.
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BibTeX
@article{egeler2026selectivity,
title = {{A selectivity filter in Tim17 mediates intramitochondrial protein sorting}},
author = {Annika Egeler and Sanjoy Paul and Rosario Valenti and Annika Nutz and Tamara Flohr and Erik Marcel Heller and Markus Räschle and Maya Schuldiner and Gerhard Hummer and Johannes M. Herrmann},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77990-3},
url = {https://www.nature.com/articles/s41467-026-77990-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A selectivity filter in Tim17 mediates intramitochondrial protein sorting
AU - Annika Egeler
AU - Sanjoy Paul
AU - Rosario Valenti
AU - Annika Nutz
AU - Tamara Flohr
AU - Erik Marcel Heller
AU - Markus Räschle
AU - Maya Schuldiner
AU - Gerhard Hummer
AU - Johannes M. Herrmann
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-77990-3
UR - https://www.nature.com/articles/s41467-026-77990-3
AB - Mitochondria import hundreds of proteins into the matrix and the inner membrane (IM). The translocase of the IM of mitochondria (TIM23 complex) sorts these proteins using topogenic signals in their structure and directs them into the matrix or inserts them into the IM. How these signals are deciphered is unknown. Here we show that Tim17, the protein-conducting subunit of the TIM23 complex, contains a highly conserved selectivity filter for incoming proteins. Using a fluorescence-based sorting reporter, we identified the mitochondrial oxidoreductase Dmo2 (akin to DMAC1 in humans) as factor for intramitochondrial protein sorting. Molecular dynamics simulations show that a Dmo2-dependent disulfide bond into Tim17 constitutes a negatively charged selectivity filter at the vestibule of the TIM23 complex that arrests membrane proteins and facilitates the lateral insertion. Our work provides a molecular rationale as to how the TIM23 translocase differentiates between soluble and membrane proteins.
SN - 2041-1723
ER -