PMID- 29093766
OWN - NLM
STAT- MEDLINE
DCOM- 20180719
LR  - 20221207
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2017
DP  - 2017
TI  - Generation and Bioenergetic Profiles of Cybrids with East Asian mtDNA 
      Haplogroups.
PG  - 1062314
LID - 10.1155/2017/1062314 [doi]
LID - 1062314
AB  - 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.
FAU - Zhou, Huaibin
AU  - Zhou H
AD  - Key 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.
FAU - Nie, Ke
AU  - Nie K
AD  - Key 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.
FAU - Qiu, Ruyi
AU  - Qiu R
AD  - Key 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.
AD  - Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang 310000, China.
FAU - Xiong, Jingting
AU  - Xiong J
AD  - Key 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.
FAU - Shao, Xiaoli
AU  - Shao X
AD  - Key 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.
FAU - Wang, Bingqian
AU  - Wang B
AD  - Key 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.
FAU - Shen, Lijun
AU  - Shen L
AD  - Key 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.
FAU - Lyu, Jianxin
AU  - Lyu J
AUID- ORCID: 0000-0001-9892-6802
AD  - Key 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.
AD  - Hangzhou Medical College, Hangzhou, Zhejiang, China.
FAU - Fang, Hezhi
AU  - Fang H
AUID- ORCID: 0000-0003-0956-3160
AD  - Key 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.
LA  - eng
PT  - Journal Article
DEP - 20170928
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Adult
MH  - Asian People
MH  - DNA, Mitochondrial/*genetics/metabolism
MH  - Energy Metabolism/*physiology
MH  - Female
MH  - Haplotypes/*physiology
MH  - Healthy Volunteers
MH  - Humans
MH  - Hybrid Cells
MH  - Male
MH  - Young Adult
PMC - PMC5637837
EDAT- 2017/11/03 06:00
MHDA- 2018/07/20 06:00
PMCR- 2017/09/28
CRDT- 2017/11/03 06:00
PHST- 2017/03/30 00:00 [received]
PHST- 2017/07/06 00:00 [revised]
PHST- 2017/08/14 00:00 [accepted]
PHST- 2017/11/03 06:00 [entrez]
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2018/07/20 06:00 [medline]
PHST- 2017/09/28 00:00 [pmc-release]
AID - 10.1155/2017/1062314 [doi]
PST - ppublish
SO  - Oxid Med Cell Longev. 2017;2017:1062314. doi: 10.1155/2017/1062314. Epub 2017 Sep 
      28.