Miga2, also known as mitoguardin-2, is a mitochondrial outer membrane protein. It is crucial for multiple cellular functions. Miga2 links mitochondria to lipid droplets (LDs) and endoplasmic reticulum (ER), promoting de novo lipogenesis in adipocytes. It also plays roles in mitochondrial quality control, autophagy, cell proliferation, and lipid transport [1,2,3,4]. It is likely essential for lipid and energy homeostasis across various cell types, and its dysregulation may impact metabolic and reproductive processes [1,3].

In adipocytes, Miga2 promotes triglyceride synthesis from non-lipid precursors, facilitating efficient lipid storage in LDs [1]. In copper-exposed hepatocytes, Miga2, carried by mitochondrial-derived vesicles (MDVs), promotes autophagosomes-lysosomes fusion by regulating ATG14 [2]. In ovarian granulosa cells, Miga2 promotes cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway, which may be related to reproductive endocrine diseases like polycystic ovary syndrome (PCOS) [3]. Also, in human ovarian granulosa cells, Miga2 is associated with hyperandrogenism and regulates steroidogenesis [5].

In conclusion, Miga2 is a multifunctional protein involved in lipid metabolism, autophagy, and cell proliferation. Its study using various models, such as in different cell types in vitro and potentially in vivo models like KO/CKO mouse models (although not explicitly detailed in the references for such models here), helps understand its role in metabolic and reproductive diseases. Insights from these studies may offer new directions for understanding disease mechanisms and potential therapeutic strategies related to lipid and energy homeostasis, as well as reproductive endocrine disorders.

References:

1. Freyre, Christophe A C, Rauher, Pascal C, Ejsing, Christer S, Klemm, Robin W. 2019. MIGA2 Links Mitochondria, the ER, and Lipid Droplets and Promotes De Novo Lipogenesis in Adipocytes. In Molecular cell, 76, 811-825.e14. doi:10.1016/j.molcel.2019.09.011. https://pubmed.ncbi.nlm.nih.gov/31628041/

2. Li, Quanwei, Guo, Pan, Wang, Shaofeng, Liao, Jianzhao, Tang, Zhaoxin. 2024. Mitochondrial derived vesicle-carrying protein MIGA2 promotes copper-induced autophagosomes-lysosomes fusion by regulating ATG14. In Journal of hazardous materials, 467, 133703. doi:10.1016/j.jhazmat.2024.133703. https://pubmed.ncbi.nlm.nih.gov/38354437/

3. 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/

4. Kim, Hyunwoo, Lee, Seowhang, Jun, Youngsoo, Lee, Changwook. 2022. Structural basis for mitoguardin-2 mediated lipid transport at ER-mitochondrial membrane contact sites. In Nature communications, 13, 3702. doi:10.1038/s41467-022-31462-6. https://pubmed.ncbi.nlm.nih.gov/35764626/

5. Yan, Ming-Qi, Wang, Yong, Wang, Zhao, Sun, Hui, Liu, Xiao-Man. 2023. Mitoguardin2 Is Associated With Hyperandrogenism and Regulates Steroidogenesis in Human Ovarian Granulosa Cells. In Journal of the Endocrine Society, 7, bvad034. doi:10.1210/jendso/bvad034. https://pubmed.ncbi.nlm.nih.gov/36936714/