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

PROCHÁZKOVÁ, Michaela, B. PANICUCCI and A. ZIKOVA. Cultured bloodstream Trypanosoma brucei adapt to life without mitochondrial translation release factor 1. Scientific reports. LONDON: NATURE PUBLISHING GROUP, 2018, vol. 8, MAR, p. 5135-5149. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/s41598-018-23472-6.

Basic information

• Original name: Cultured bloodstream Trypanosoma brucei adapt to life without mitochondrial translation release factor 1
• Authors: PROCHÁZKOVÁ, Michaela (203 Czech Republic, guarantor, belonging to the institution), B. PANICUCCI (203 Czech Republic) and A. ZIKOVA (203 Czech Republic).
• Edition: Scientific reports, LONDON, NATURE PUBLISHING GROUP, 2018, 2045-2322.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10607 Virology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 4.011
• RIV identification code: RIV/00216224:14740/18:00106576
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1038/s41598-018-23472-6
• UT WoS: 000428163600006
• Keywords in English: PEPTIDYL-TRANSFER-RNA; RIBOSOMAL-PROTEIN S12; HUMAN ATP SYNTHASE; LEISHMANIA-TARENTOLAE; KINETOPLAST DNA; ALTERNATIVE OXIDASE; SECONDARY STRUCTURE; ADP/ATP CARRIER; MAXICIRCLE DNA; INNER MEMBRANE
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

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.