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The ADP/ATP carrier and its relationship to oxidative phosphorylation in ancestral protist trypanosoma brucei
A. Gnipová, K. Šubrtová, B. Panicucci, A. Horváth, J. Lukeš, A. Zíková,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2002 to 2015
Freely Accessible Science Journals
from 2002 to 2015
PubMed Central
from 2002 to 2015
Europe PubMed Central
from 2002 to 2015
Open Access Digital Library
from 2002-02-01
PubMed
25616281
DOI
10.1128/ec.00238-14
Knihovny.cz E-resources
- MeSH
- Mitochondrial ADP, ATP Translocases chemistry genetics metabolism MeSH
- Evolution, Molecular * MeSH
- Oxidative Phosphorylation * MeSH
- Protozoan Proteins chemistry genetics metabolism MeSH
- Trypanosoma brucei brucei genetics metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The highly conserved ADP/ATP carrier (AAC) is a key energetic link between the mitochondrial (mt) and cytosolic compartments of all aerobic eukaryotic cells, as it exchanges the ATP generated inside the organelle for the cytosolic ADP. Trypanosoma brucei, a parasitic protist of medical and veterinary importance, possesses a single functional AAC protein (TbAAC) that is related to the human and yeast ADP/ATP carriers. However, unlike previous studies performed with these model organisms, this study showed that TbAAC is most likely not a stable component of either the respiratory supercomplex III+IV or the ATP synthasome but rather functions as a physically separate entity in this highly diverged eukaryote. Therefore, TbAAC RNA interference (RNAi) ablation in the insect stage of T. brucei does not impair the activity or arrangement of the respiratory chain complexes. Nevertheless, RNAi silencing of TbAAC caused a severe growth defect that coincides with a significant reduction of mt ATP synthesis by both substrate and oxidative phosphorylation. Furthermore, TbAAC downregulation resulted in a decreased level of cytosolic ATP, a higher mt membrane potential, an elevated amount of reactive oxygen species, and a reduced consumption of oxygen in the mitochondria. Interestingly, while TbAAC has previously been demonstrated to serve as the sole ADP/ATP carrier for ADP influx into the mitochondria, our data suggest that a second carrier for ATP influx may be present and active in the T. brucei mitochondrion. Overall, this study provides more insight into the delicate balance of the functional relationship between TbAAC and the oxidative phosphorylation (OXPHOS) pathway in an early diverged eukaryote.
Biology Center Institute of Parasitology Czech Academy of Sciences České Budějovice Czech Republic
Department of Biochemistry Faculty of Natural Sciences Comenius University Bratislava Slovakia
References provided by Crossref.org
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