Projects per year
Abstract
Anti-trypanosomal drugs, used to tackle lethal human and animal diseases, target an unusual parasite DNA structure in a cellular compartment known as the mitochondrion. Using a high-throughput genetic approach to study drug resistance, we identified every component of a molecular rotor that couples ATP hydrolysis to proton transport across non-mitochondrial membranes. Surprisingly, this molecular machine was found to communicate with a related mitochondrial rotor and, when defective, rendered the mitochondrial DNA structure obsolete. Our findings reveal new potential mechanisms of multidrug resistance in trypanosomes. They also suggest that communication between these rotors in two separate cellular compartments could be conserved through evolution, reflecting an unanticipated and important aspect of environmental sensing and metabolic control in nucleated cells.
Original language | English |
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Pages (from-to) | 9112-9117 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 112 |
Issue number | 29 |
DOIs | |
Publication status | Published - 21 Jul 2015 |
Keywords
- Brucei
- Mitochondrion
- Nagana
- Petite
- Samorin
ASJC Scopus subject areas
- General
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Dive into the research topics of 'Vacuolar ATPase depletion affects mitochondrial ATPase function, kinetoplast dependency, and drug sensitivity in trypanosomes'. Together they form a unique fingerprint.Projects
- 1 Finished
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High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
Horn, D. (Investigator)
1/09/13 → 29/02/20
Project: Research
Student theses
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VSG expression in African trypanosomes: Gene silencing, cell cycle and developmental control
Hutchinson, S. J. (Author), Horn, D. (Supervisor), 2016Student thesis: Doctoral Thesis › Doctor of Philosophy
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