Miga1, also known as Mitoguardin 1, is a mitochondrial outer-membrane protein-encoding gene. It plays a crucial role in mitochondrial dynamics, specifically promoting mitochondrial fusion. Miga1 is involved in various biological processes, including cell proliferation, oocyte maturation, and ovarian endocrine functions. It is associated with pathways such as the Hippo-YAP1 signaling pathway and may regulate protein kinase B (AKT) activity [1,3,4].

Knockout mouse models of Miga1 and its homolog Miga2 (Miga1/2 -/-) have revealed significant impacts. In females, these knockouts lead to greatly reduced oocyte and early embryo quality, resulting in subfertility. Mitochondria in oocytes show abnormal clustering, increased reactive oxygen species production, damaged ultrastructures, reduced ATP production, decreased mitochondrial-DNA copy number, and lower mitochondrial membrane potential during meiotic maturation. These changes cause low polar-body extrusion rates during oocyte maturation and reduced early embryo developmental potential [3]. In granulosa cells, Miga1/2-knockout leads to severe defects in luteinization and steroidogenesis, as well as disordered mitochondrial morphology and function in response to gonadotropins [4]. In differentiated adipocytes, Miga1 down-regulation leads to mitochondrial dysfunction, with lower oxygen consumption and reduced UCP1 expression, suggesting its role in fat distribution [2,5].

In conclusion, Miga1 is essential for maintaining mitochondrial functions, ensuring oocyte maturation, and regulating ovarian endocrine functions. The Miga1/2 knockout mouse models have provided valuable insights into its role in female subfertility. Additionally, its role in mitochondrial function in adipocytes indicates its potential involvement in fat-related metabolic disorders [2,3,4,5].