Functional differences between mitochondrial haplogroup T and haplogroup H in HEK293 cybrid cells

PLoS One. 2012;7(12):e52367. doi: 10.1371/journal.pone.0052367. Epub 2012 Dec 26.


Background: Epidemiological case-control studies have revealed associations between mitochondrial haplogroups and the onset and/or progression of various multifactorial diseases. For instance, mitochondrial haplogroup T was previously shown to be associated with vascular diseases, including coronary artery disease and diabetic retinopathy. In contrast, haplogroup H, the most frequent haplogroup in Europe, is often found to be more prevalent in healthy control subjects than in patient study groups. However, justifications for the assumption that haplogroups are functionally distinct are rare. Therefore, we attempted to compare differences in mitochondrial function between haplogroup H and T cybrids.

Methodology/principal findings: Mitochondrial haplogroup H and T cybrids were generated by fusion of HEK293 cells devoid of mitochondrial DNA with isolated thrombocytes of individuals with the respective haplogroups. These cybrid cells were analyzed for oxidative phosphorylation (OXPHOS) enzyme activities, mitochondrial DNA (mtDNA) copy number, growth rate and susceptibility to reactive oxygen species (ROS). We observed that haplogroup T cybrids have higher survival rate when challenged with hydrogen peroxide, indicating a higher capability to cope with oxidative stress.

Conclusions/significance: The results of this study show that functional differences exist between HEK293 cybrid cells which differ in mitochondrial genomic background.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • DNA, Mitochondrial / genetics
  • Gene Dosage / genetics
  • HEK293 Cells / cytology*
  • HEK293 Cells / metabolism
  • Haplotypes*
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Oxidative Phosphorylation
  • Oxidative Stress / genetics


  • DNA, Mitochondrial

Grant support

The study was supported by a grant from the Paracelsus Medical University Salzburg (R-10/05/020-MUE)( and by the “Vereinigung zur Förderung Pädiatrischer Forschung und Fortbildung, Salzburg” ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.