Interconnections with and within the trypanosomal respiratory chain revealed by complexome profiling
- 1Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czechia
Abstract
Proteins are frequently integrated into multicomponent complexes that execute the elaborate processes supporting life. Thus, a protein's function can only be defined by the company it keeps within a complex. Proteomes provide informative protein inventories but lack information about protein quaternary structures. Complexome profiling (CP) has been transformative in capturing the comprehensive population structure of complexes at a given moment within a cell. We have employed CP to chart the multiprotein complex landscape of two life cycle stages of Trypanosoma brucei. These data have allowed the observation of previously hidden interactions with and within the mitochondrial respiratory chain. We have found (1) an exceptional case of a SLC25 solute transporter that interacts with NADH dehydrogenase, (2) two ATP synthase subunit g paralogs that are intriguingly excluded from the enzyme's dimers, and (3) refined the known composition of ubiquinol:cytochrome c oxidoreductase by addition of missing subunits and removing an incorrectly assigned subunit, which more likely acts to insert the iron-sulfur co-factor into the complex. Further investigation into ubiquinol:cytochrome c oxidoreductase assembly revealed crosstalk between incorporation of its nuclear subunits with mitochondrial translation, possibly facilitating a hitherto unknown quality control mechanism. These discoveries demonstrate the power of our CP data for generation and testing of hypotheses about the mitochondrial and other organellar multiprotein complexes of T. brucei, a protist of medical and evolutionary importance.
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BibTeX
@misc{benz2026interconnections,
title = {{Interconnections with and within the trypanosomal respiratory chain revealed by complexome profiling}},
author = {C. Benz and R. T. Khan and M. Hammond and O. Gahura and U. Koblar and L. R. Cadena and I. Skodova-Sverakova and P. T. Butterill and M. Vrbacky and H. Hashimi},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.08.750046},
url = {https://www.biorxiv.org/content/10.64898/2026.09.08.750046v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Interconnections with and within the trypanosomal respiratory chain revealed by complexome profiling
AU - C. Benz
AU - R. T. Khan
AU - M. Hammond
AU - O. Gahura
AU - U. Koblar
AU - L. R. Cadena
AU - I. Skodova-Sverakova
AU - P. T. Butterill
AU - M. Vrbacky
AU - H. Hashimi
PY - 2026
DA - 2026/09/08
PB - bioRxiv
DO - 10.64898/2026.09.08.750046
UR - https://www.biorxiv.org/content/10.64898/2026.09.08.750046v1
AB - Proteins are frequently integrated into multicomponent complexes that execute the elaborate processes supporting life. Thus, a protein's function can only be defined by the company it keeps within a complex. Proteomes provide informative protein inventories but lack information about protein quaternary structures. Complexome profiling (CP) has been transformative in capturing the comprehensive population structure of complexes at a given moment within a cell. We have employed CP to chart the multiprotein complex landscape of two life cycle stages of Trypanosoma brucei. These data have allowed the observation of previously hidden interactions with and within the mitochondrial respiratory chain. We have found (1) an exceptional case of a SLC25 solute transporter that interacts with NADH dehydrogenase, (2) two ATP synthase subunit g paralogs that are intriguingly excluded from the enzyme's dimers, and (3) refined the known composition of ubiquinol:cytochrome c oxidoreductase by addition of missing subunits and removing an incorrectly assigned subunit, which more likely acts to insert the iron-sulfur co-factor into the complex. Further investigation into ubiquinol:cytochrome c oxidoreductase assembly revealed crosstalk between incorporation of its nuclear subunits with mitochondrial translation, possibly facilitating a hitherto unknown quality control mechanism. These discoveries demonstrate the power of our CP data for generation and testing of hypotheses about the mitochondrial and other organellar multiprotein complexes of T. brucei, a protist of medical and evolutionary importance.
ER -