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

0498799 - BC 2019 RIV GB eng J - Článek v odborném periodiku
Procházková, Michaela - Panicucci, Brian - Zíková, Alena
Cultured bloodstream Trypanosoma brucei adapt to life without mitochondrial translation release factor 1.
Scientific Reports. Roč. 8, MAR 23 (2018), č. článku 5135. ISSN 2045-2322. E-ISSN 2045-2322
Grant CEP: GA MŠMT(CZ) LL1205; GA MŠMT(CZ) EF16_019/0000759
GRANT EU: Foundation for Science and Technology(XE) 1965
Institucionální podpora: RVO:60077344
Klíčová slova: PEPTIDYL-TRANSFER-RNA * RIBOSOMAL-PROTEIN S12 * HUMAN ATP SYNTHASE * LEISHMANIA-TARENTOLAE * KINETOPLAST DNA * ALTERNATIVE OXIDASE * SECONDARY STRUCTURE * ADP/ATP CARRIER * MAXICIRCLE DNA * INNER MEMBRANE
Obor OECD: Microbiology
Impakt faktor: 4.011, rok: 2018
https://www.nature.com/articles/s41598-018-23472-6

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.
Trvalý link: http://hdl.handle.net/11104/0291074