Protective Effect of Mitochondrial ND2 C5178A Gene Mutation on Cell and Mitochondrial Functions

Author:

Tian Liuyang12ORCID,Zhu Chao23,Yang Huanwan2,Li Yang2,Liu Yuqi2456ORCID

Affiliation:

1. School of Medicine, Nankai University, Tianjin 300071, China

2. Cardiac Department, The Institute of Geriatric Cardiology PLA General Hospital, Beijing 100853, China

3. Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China

4. Department of Cardiology & National Clinical Research Center of Geriatrics Disease, Chinese PLA General Hospital, Beijing 100853, China

5. Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA General Hospital, Beijing 100853, China

6. National Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China

Abstract

Background. Mitochondrial NADH dehydrogenase subunit 2 (MT-ND2) m. 5178C>A gene mutation has protective effects against various diseases, but the molecular mechanism is still unclear. In previous study, we found a heteroplasmy level of MT-ND2 m. 5178C>A mutation in normotensive controls. Peripheral blood samples were obtained from essential hypertension individuals carrying the mutation and healthy controls without gene mutation to establish immortalized lymphocyte lines. To investigate the effect of the MT-ND2 m. 5178C>A gene mutation, comparative analyses of the two group cell lines were performed, including measurements of cell proliferation, viability, ATP synthesis, mitochondrial oxidative stress, and oxidative phosphorylation. Results. The cell proliferation rate and viability of the MT-ND2 m. 5178C>A mutant lymphocyte line were higher than those of the control group. Mitochondrial functions of the MT-ND2 m. 5178C>A mutant lymphocyte were increased, including increased ATP synthesis, decreased ROS production, increased mitochondrial membrane potential and Bcl-2 gene transcription and protein translation, decreased Caspase 3/7 activity, and decreased early apoptosis and late apoptosis. The oxygen consumption rate (OCR) of the mutant lymphocyte line was higher than that of the control group, including basal OCR, ATP-linked OCR, maximal OCR, proton leak OCR, and reserve OCR, and there was no significant difference in nonmitochondrial OCR. The activity of Mitochondrial Complex I of the mutant group was increased than that of the control group. Conclusions. The MT-ND2 m. 5178C>A mutation is a protective mutation that may be related to improvement of mitochondrial functions and decrease in apoptosis.

Funder

Beijing Nova Program

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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