Publication details

Cultured bloodstream Trypanosoma brucei adapt to life without mitochondrial translation release factor 1

Authors

PROCHÁZKOVÁ Michaela PANICUCCI B. ZIKOVA A.

Type Article in Periodical
Magazine / Source Scientific reports
MU Faculty or unit

Central European Institute of Technology

Citation
Doi http://dx.doi.org/10.1038/s41598-018-23472-6
Keywords PEPTIDYL-TRANSFER-RNA; RIBOSOMAL-PROTEIN S12; HUMAN ATP SYNTHASE; LEISHMANIA-TARENTOLAE; KINETOPLAST DNA; ALTERNATIVE OXIDASE; SECONDARY STRUCTURE; ADP/ATP CARRIER; MAXICIRCLE DNA; INNER MEMBRANE
Description Trypanosoma brucei is an extracellular parasite that alternates between an insect vector (procyclic form) and the bloodstream of a mammalian host (bloodstream form). While it was previously reported that mitochondrial release factor 1 (TbMrf1) is essential in cultured procyclic form cells, we demonstrate here that in vitro bloodstream form cells can tolerate the elimination of TbMrf1. Therefore, we explored if this discrepancy is due to the unique bioenergetics of the parasite since procyclic form cells rely on oxidative phosphorylation; whereas bloodstream form cells utilize glycolysis for ATP production and FoF1-ATPase to maintain the essential mitochondrial membrane potential. The observed disruption of intact bloodstream form FoF1-ATPases serves as a proxy to indicate that the translation of its mitochondrially encoded subunit A6 is impaired without TbMrf1. While these null mutants have a decreased mitochondrial membrane potential, they have adapted by increasing their dependence on the electrogenic contributions of the ADP/ATP carrier to maintain the mitochondrial membrane potential above the minimum threshold required for T. brucei viability in vitro. However, this inefficient compensatory mechanism results in avirulent mutants in mice. Finally, the depletion of the codon-independent release factor TbPth4 in the TbMrf1 knockouts further exacerbates the characterized mitchondrial phenotypes.