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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 1062314, 12 pages
https://doi.org/10.1155/2017/1062314
Research Article

Generation and Bioenergetic Profiles of Cybrids with East Asian mtDNA Haplogroups

1Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
2Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang 310000, China
3Hangzhou Medical College, Hangzhou, Zhejiang, China

Correspondence should be addressed to Jianxin Lyu; moc.361@313ulxj and Hezhi Fang; nc.ude.umw@hgnaf

Received 30 March 2017; Revised 6 July 2017; Accepted 14 August 2017; Published 28 September 2017

Academic Editor: Icksoo Lee

Copyright © 2017 Huaibin Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human mitochondrial DNA (mtDNA) variants and haplogroups may contribute to susceptibility to various diseases and pathological conditions, but the underlying mechanisms are not well understood. To address this issue, we established a cytoplasmic hybrid (cybrid) system to investigate the role of mtDNA haplogroups in human disease; specifically, we examined the effects of East Asian mtDNA genetic backgrounds on oxidative phosphorylation (OxPhos). We found that mtDNA single nucleotide polymorphisms such as m.489T>C, m.10398A>G, m.10400C>T, m.C16223T, and m.T16362C affected mitochondrial function at the level of mtDNA, mtRNA, or the OxPhos complex. Macrohaplogroup M exhibited higher respiratory activity than haplogroup N owing to its higher mtDNA content, mtRNA transcript levels, and complex III abundance. Additionally, haplogroup M had higher reactive oxygen species levels and NAD+/NADH ratios than haplogroup N, suggesting difference in mitonuclear interactions. Notably, subhaplogroups G2, B4, and F1 appeared to contribute significantly to the differences between haplogroups M and N. Thus, our cybrid-based system can provide insight into the mechanistic basis for the role of mtDNA haplogroups in human diseases and the effect of mtDNA variants on mitochondrial OxPhos function. In addition, studies of mitonuclear interaction using this system can reveal predisposition to certain diseases conferred by variations in mtDNA.