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Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.

Publication ,  Journal Article
Dingley, SD; Polyak, E; Ostrovsky, J; Srinivasan, S; Lee, I; Rosenfeld, AB; Tsukikawa, M; Xiao, R; Selak, MA; Coon, JJ; Hebert, AS; Kwon, YJ ...
Published in: J Mol Biol
May 29, 2014

Mitochondrial DNA (mtDNA) sequence variation can influence the penetrance of complex diseases and climatic adaptation. While studies in geographically defined human populations suggest that mtDNA mutations become fixed when they have conferred metabolic capabilities optimally suited for a specific environment, it has been challenging to definitively assign adaptive functions to specific mtDNA sequence variants in mammals. We investigated whether mtDNA genome variation functionally influences Caenorhabditis elegans wild isolates of distinct mtDNA lineages and geographic origins. We found that, relative to N2 (England) wild-type nematodes, CB4856 wild isolates from a warmer native climate (Hawaii) had a unique p.A12S amino acid substitution in the mtDNA-encoded COX1 core catalytic subunit of mitochondrial complex IV (CIV). Relative to N2, CB4856 worms grown at 20°C had significantly increased CIV enzyme activity, mitochondrial matrix oxidant burden, and sensitivity to oxidative stress but had significantly reduced lifespan and mitochondrial membrane potential. Interestingly, mitochondrial membrane potential was significantly increased in CB4856 grown at its native temperature of 25°C. A transmitochondrial cybrid worm strain, chpIR (M, CB4856>N2), was bred as homoplasmic for the CB4856 mtDNA genome in the N2 nuclear background. The cybrid strain also displayed significantly increased CIV activity, demonstrating that this difference results from the mtDNA-encoded p.A12S variant. However, chpIR (M, CB4856>N2) worms had significantly reduced median and maximal lifespan relative to CB4856, which may relate to their nuclear-mtDNA genome mismatch. Overall, these data suggest that C. elegans wild isolates of varying geographic origins may adapt to environmental challenges through mtDNA variation to modulate critical aspects of mitochondrial energy metabolism.

Duke Scholars

Published In

J Mol Biol

DOI

EISSN

1089-8638

Publication Date

May 29, 2014

Volume

426

Issue

11

Start / End Page

2199 / 2216

Location

Netherlands

Related Subject Headings

  • Models, Molecular
  • Mitochondria
  • Male
  • Geography
  • Genetic Variation
  • Energy Metabolism
  • Electron Transport Complex IV
  • DNA, Mitochondrial
  • Cell Respiration
  • Caenorhabditis elegans Proteins
 

Citation

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Dingley, S. D., Polyak, E., Ostrovsky, J., Srinivasan, S., Lee, I., Rosenfeld, A. B., … Falk, M. J. (2014). Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans. J Mol Biol, 426(11), 2199–2216. https://doi.org/10.1016/j.jmb.2014.02.009
Dingley, Stephen D., Erzsebet Polyak, Julian Ostrovsky, Satish Srinivasan, Icksoo Lee, Amy B. Rosenfeld, Mai Tsukikawa, et al. “Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.J Mol Biol 426, no. 11 (May 29, 2014): 2199–2216. https://doi.org/10.1016/j.jmb.2014.02.009.
Dingley SD, Polyak E, Ostrovsky J, Srinivasan S, Lee I, Rosenfeld AB, et al. Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans. J Mol Biol. 2014 May 29;426(11):2199–216.
Dingley, Stephen D., et al. “Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.J Mol Biol, vol. 426, no. 11, May 2014, pp. 2199–216. Pubmed, doi:10.1016/j.jmb.2014.02.009.
Dingley SD, Polyak E, Ostrovsky J, Srinivasan S, Lee I, Rosenfeld AB, Tsukikawa M, Xiao R, Selak MA, Coon JJ, Hebert AS, Grimsrud PA, Kwon YJ, Pagliarini DJ, Gai X, Schurr TG, Hüttemann M, Nakamaru-Ogiso E, Falk MJ. Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans. J Mol Biol. 2014 May 29;426(11):2199–2216.
Journal cover image

Published In

J Mol Biol

DOI

EISSN

1089-8638

Publication Date

May 29, 2014

Volume

426

Issue

11

Start / End Page

2199 / 2216

Location

Netherlands

Related Subject Headings

  • Models, Molecular
  • Mitochondria
  • Male
  • Geography
  • Genetic Variation
  • Energy Metabolism
  • Electron Transport Complex IV
  • DNA, Mitochondrial
  • Cell Respiration
  • Caenorhabditis elegans Proteins