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Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. / Dean, Samuel; Gould, Matthew K.; Dewar, Caroline E. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 36, 03.09.2013, p. 14741-14746.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Dean, S, Gould, MK, Dewar, CE & Schnaufer, AC 2013, 'Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 36, pp. 14741-14746. https://doi.org/10.1073/PNAS.1305404110

APA

Dean, S., Gould, M. K., Dewar, C. E., & Schnaufer, A. C. (2013). Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. Proceedings of the National Academy of Sciences of the United States of America, 110(36), 14741-14746. https://doi.org/10.1073/PNAS.1305404110

Vancouver

Dean S, Gould MK, Dewar CE, Schnaufer AC. Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. Proceedings of the National Academy of Sciences of the United States of America. 2013 Sept 3;110(36):14741-14746. Epub 2013 Aug 19. doi: 10.1073/PNAS.1305404110

Author

Dean, Samuel ; Gould, Matthew K. ; Dewar, Caroline E. et al. / Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 36. pp. 14741-14746.

Bibtex

@article{281b6d0ae34c488ea07993d0649f5777,
title = "Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes",
abstract = "Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens T. evansi and T. equiperdum are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F1FO–ATPase subunit γ can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing FO-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of T. brucei, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F1FO–ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites.",
author = "Samuel Dean and Gould, {Matthew K.} and Dewar, {Caroline E.} and Schnaufer, {Achim C.}",
year = "2013",
month = sep,
day = "3",
doi = "10.1073/PNAS.1305404110",
language = "English",
volume = "110",
pages = "14741--14746",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "36",

}

RIS

TY - JOUR

T1 - Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes

AU - Dean, Samuel

AU - Gould, Matthew K.

AU - Dewar, Caroline E.

AU - Schnaufer, Achim C.

PY - 2013/9/3

Y1 - 2013/9/3

N2 - Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens T. evansi and T. equiperdum are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F1FO–ATPase subunit γ can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing FO-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of T. brucei, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F1FO–ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites.

AB - Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei depends on maintenance and expression of its kinetoplast (kDNA), the mitochondrial genome of this parasite and a putative target for veterinary and human antitrypanosomatid drugs. However, the closely related animal pathogens T. evansi and T. equiperdum are transmitted independently of tsetse flies and survive without a functional kinetoplast for reasons that have remained unclear. Here, we provide definitive evidence that single amino acid changes in the nuclearly encoded F1FO–ATPase subunit γ can compensate for complete physical loss of kDNA in these parasites. Our results provide insight into the molecular mechanism of compensation for kDNA loss by showing FO-independent generation of the mitochondrial membrane potential with increased dependence on the ADP/ATP carrier. Our findings also suggest that, in the pathogenic bloodstream stage of T. brucei, the huge and energetically demanding apparatus required for kDNA maintenance and expression serves the production of a single F1FO–ATPase subunit. These results have important implications for drug discovery and our understanding of the evolution of these parasites.

UR - https://publons.com/wos-op/publon/71745908/

U2 - 10.1073/PNAS.1305404110

DO - 10.1073/PNAS.1305404110

M3 - Journal article

VL - 110

SP - 14741

EP - 14746

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 36

ER -