TargetMITO: a rule-based model for generating functional synthetic mitochondrial targeting sequences in yeast
- 1Manchester Institute of Biotechnology, University of Manchester , 131 Princess Street, M1 7DN, Manchester ,
- 2CNRS, IBGC , UMR 5095, University of Bordeaux, F-33000 Bordeaux ,
Abstract
Mitochondria are essential organelles containing their own genomes, encoding a few proteins essential for energy production. Most of the mitochondrial proteins are nucleus-encoded, translated as precursors in the cytosol, with a large fraction of these precursors properly addressed by an N-terminal mitochondrial targeting sequence (MTS). These MTS share common features but no consensus sequence can explain their functionality nor the precursors-specific determinants of mitochondrial import. To help understand this mechanism, we created a simple computational model to generate functional synthetic MTS while maintaining a tight control on the design parameters. Using the budding yeast, we demonstrated the presence of precursors-specific import capabilities in addressing artificially nucleus-relocated OXPHOS proteins. Our research confirms the existence of cargo-dependent functional compatibilities and takes us one step closer towards improving gene therapy-based treatment of mitochondrial diseases.
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BibTeX
@article{gombeau2026targetmito,
title = {{TargetMITO: a rule-based model for generating functional synthetic mitochondrial targeting sequences in yeast}},
author = {Kewin Gombeau and Raymond Wan and Joshua S James and Déborah Tribouillard-Tanvier and Yizhi Cai},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag986},
url = {https://academic.oup.com/nar/article/doi/10.1093/nar/gkag986/8959888},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TargetMITO: a rule-based model for generating functional synthetic mitochondrial targeting sequences in yeast
AU - Kewin Gombeau
AU - Raymond Wan
AU - Joshua S James
AU - Déborah Tribouillard-Tanvier
AU - Yizhi Cai
PY - 2026
DA - 2026/10/01
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag986
UR - https://academic.oup.com/nar/article/doi/10.1093/nar/gkag986/8959888
AB - Mitochondria are essential organelles containing their own genomes, encoding a few proteins essential for energy production. Most of the mitochondrial proteins are nucleus-encoded, translated as precursors in the cytosol, with a large fraction of these precursors properly addressed by an N-terminal mitochondrial targeting sequence (MTS). These MTS share common features but no consensus sequence can explain their functionality nor the precursors-specific determinants of mitochondrial import. To help understand this mechanism, we created a simple computational model to generate functional synthetic MTS while maintaining a tight control on the design parameters. Using the budding yeast, we demonstrated the presence of precursors-specific import capabilities in addressing artificially nucleus-relocated OXPHOS proteins. Our research confirms the existence of cargo-dependent functional compatibilities and takes us one step closer towards improving gene therapy-based treatment of mitochondrial diseases.
SN - 0305-1048
SN - 1362-4962
ER -