Oncotarget

Research Papers: Pathology:

Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions

Xiao-Man Liu, Yong-Ping Zhang, Shu-Yan Ji, Bo-Tai Li, Xuejun Tian, Dali Li, Chao Tong and Heng-Yu Fan _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:1155-1167. https://doi.org/10.18632/oncotarget.6713

Metrics: PDF 2158 views  |   HTML 1623 views  |   ?  


Abstract

Xiao-Man Liu1, Yong-Ping Zhang1, Shu-Yan Ji1, Bo-Tai Li1, Xuejun Tian1, Dali Li2, Chao Tong1 and Heng-Yu Fan1

1 Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China

2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

Correspondence to:

Heng-Yu Fan, email:

Chao Tong, email:

Keywords: mitochondrion, ROS, mtDNA copy number, oocyte meiosis, female infertility, Pathology Section

Received: October 02, 2015 Accepted: December 09, 2015 Published: December 21, 2015

Abstract

Mitochondrial dynamics change mitochondrial morphological features and numbers as a part of adaptive cellular metabolism, which is vital for most eukaryotic cells and organisms. A disease or even death of an animal can occur if these dynamics are disrupted. Using large-scale genetic screening in fruit flies, we previously found the gene mitoguardin (Miga), which encodes a mitochondrial outer-membrane protein and promotes mitochondrial fusion. Knockout mouse strains were generated for the mammalian Miga homologs Miga1 and Miga2. Miga1/2-/- females show greatly reduced quality of oocytes and early embryos and are subfertile. Mitochondria became clustered in the cytoplasm of oocytes from the germinal-vesicle stage to meiosis II; production of reactive oxygen species increased in mitochondria and caused damage to mitochondrial ultrastructures. Additionally, reduced ATP production, a decreased mitochondrial-DNA copy number, and lower mitochondrial membrane potential were detected in Miga1/2-/- oocytes during meiotic maturation. These changes resulted in low rates of polar-body extrusion during oocyte maturation, reduced developmental potential of the resulting early embryos, and consequently female subfertility. We provide direct evidence that MIGA1/2-regulated mitochondrial dynamics is crucial for mitochondrial functions, ensure oocyte maturation, and maintain the developmental potential.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 6713