Projects per year
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.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 21 Jul 2015|
ASJC Scopus subject areas
FingerprintDive 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.
- 1 Finished
High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
1/09/13 → 29/02/20
Supervisor: Horn, D. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy