Miga1, also known as mitoguardin 1, is a mitochondrial protein that plays a crucial role in mitochondrial fusion, mitochondria-endoplasmic reticulum contacts, lipid formation, and autophagy [3,4,5]. It is involved in pathways related to cell proliferation, such as the Hippo-YAP1 signaling pathway and regulation of protein kinase B (AKT) activity [1]. Miga1 is important for ovarian endocrine functions, follicular development, and may also have implications in adipocyte processes related to body fat distribution [1,2].

Knockout mouse models of Miga1 and its homolog Miga2 have shown that female mice with Miga1/2 knockout are subfertile. Ovarian granulosa cells from these knockout mice exhibit severe defects in luteinization, steroidogenesis, and disordered mitochondrial morphology and function in response to gonadotropins [3]. In differentiated adipocytes, Miga1 down-regulation led to mitochondrial dysfunction [2].

In conclusion, Miga1 is essential for maintaining mitochondrial functions, which are crucial for ovarian endocrine functions and ovulation, as well as for adipocyte function and potentially body fat distribution. The use of Miga1 knockout mouse models has provided valuable insights into its role in these processes, which may contribute to understanding the molecular pathogenesis of reproductive endocrine diseases like polycystic ovary syndrome (PCOS) [1,3].

References:

1. Yan, Ming-Qi, Zhu, Bing-Hong, Liu, Xiao-Hong, Li, Tao, Liu, Xiao-Man. 2023. Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway. In Cell death & disease, 14, 779. doi:10.1038/s41419-023-06312-y. https://pubmed.ncbi.nlm.nih.gov/38012141/

2. Reed, Jordan N, Huang, Jiansheng, Li, Yong, Björkegren, Johan Lm, Civelek, Mete. 2024. Systems genetics analysis of human body fat distribution genes identifies adipocyte processes. In Life science alliance, 7, . doi:10.26508/lsa.202402603. https://pubmed.ncbi.nlm.nih.gov/38702075/

3. Liu, Xiao-Man, Zhang, Yin-Li, Ji, Shu-Yan, Tong, Chao, Fan, Heng-Yu. . Mitochondrial Function Regulated by Mitoguardin-1/2 Is Crucial for Ovarian Endocrine Functions and Ovulation. In Endocrinology, 158, 3988-3999. doi:10.1210/en.2017-00487. https://pubmed.ncbi.nlm.nih.gov/28938432/

4. Liu, Xiao-Man, Zhang, Yong-Ping, Ji, Shu-Yan, Tong, Chao, Fan, Heng-Yu. . Mitoguardin-1 and -2 promote maturation and the developmental potential of mouse oocytes by maintaining mitochondrial dynamics and functions. In Oncotarget, 7, 1155-67. doi:10.18632/oncotarget.6713. https://pubmed.ncbi.nlm.nih.gov/26716412/

5. Zhang, Yongping, Liu, Xiaoman, Bai, Jian, Fan, Heng-Yu, Tong, Chao. 2015. Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis. In Molecular cell, 61, 111-24. doi:10.1016/j.molcel.2015.11.017. https://pubmed.ncbi.nlm.nih.gov/26711011/