title: Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions.
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.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Ji
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Bo-Tai
authors.initials: BT
authors.lastname: Li
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Tian
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Fan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D061209:Proton Ionophores / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D061209:Proton Ionophores; D017382:Reactive Oxygen Species; C000612422:mitoguardin-1 protein, mouse; C000612423:mitoguardin-2 protein, mouse; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate
keywords: Pathology Section; ROS; female infertility; mitochondrion; mtDNA copy number; oocyte meiosis