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.
Highlights
In mammalian females, oocytes are arrested at the germinal vesicle (GV) stage of meiosis I and are stored in ovarian follicles for years or even decades
Oocyte energy metabolism increases due to the requirements of multiple physiological events, such as GV breakdown (GVBD), spindle formation, chromosome alignment and separation, and polar-body extrusion (PBE) [2]
Mitochondrial functions strongly correlate with mitochondrial structure and morphology [22, 23]
Summary
Oocytes are arrested at the germinal vesicle (GV) stage of meiosis I and are stored in ovarian follicles for years or even decades. Insulin www.impactjournals.com/oncotarget resistance was found to disrupt mitochondrial function by reducing mtDNA copy numbers and ATP levels in mouse MII oocytes. MIGA1/2 regulate mitochondrial dynamics and functions during oocyte meiosis and embryonic development.
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