Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
PLoS One. 2012;7(12):e52367. doi: 10.1371/journal.pone.0052367. Epub 2012 Dec 26.
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.
流行病学病例对照研究揭示了线粒体单倍群与各种多因素疾病的发病和/或进展之间的关联。例如，线粒体单倍群 T 先前被显示与血管疾病有关，包括冠状动脉疾病和糖尿病性视网膜病变。相比之下，在欧洲最常见的单倍群 H 通常在健康对照组中比在患者研究组中更为普遍。然而，很少有理由假设单倍群在功能上是不同的。因此，我们试图比较单倍群 H 和 T 细胞杂种之间线粒体功能的差异。
方法/主要发现：通过将缺乏线粒体 DNA 的 HEK293 细胞与具有各自单倍群的个体的分离血小板融合，产生了线粒体单倍群 H 和 T 细胞杂种。分析了这些细胞杂种的氧化磷酸化 (OXPHOS) 酶活性、线粒体 DNA (mtDNA) 拷贝数、生长速度和对活性氧 (ROS) 的敏感性。我们观察到，当受到过氧化氢的挑战时，单倍群 T 细胞杂种的存活率更高，这表明它们具有更高的应对氧化应激的能力。
结论/意义：这项研究的结果表明，在线粒体基因组背景不同的 HEK293 细胞杂种之间存在功能差异。
