MIGA2, also known as mitoguardin-2, is a mitochondrial outer membrane protein. It is crucial for multiple cellular functions, including lipid metabolism, mitochondrial dynamics, and organelle-to-organelle communication. MIGA2 links mitochondria, the endoplasmic reticulum (ER), and lipid droplets, promoting de novo lipogenesis in adipocytes, which is essential for lipid and energy homeostasis in various cell types [1]. It also plays a role in mitochondrial quality control, autophagy, cell proliferation, and steroidogenesis, and is associated with pathways like Hippo-YAP1 and processes related to copper-induced autophagy [2,3,5]. Genetic models can help further explore its functions.

In adipocytes, MIGA2 binds to VAP-A or VAP-B in the ER and contains an amphipathic LD-targeting motif, facilitating efficient lipid storage in LDs [1]. In hepatocytes, copper exposure promotes MDVs secretion with increased MIGA2 in MDVs, and MIGA2 promotes copper-induced autophagosomes-lysosomes fusion by regulating ATG14 [2]. In ovarian granulosa cells, MIGA2 promotes cell proliferation, regulates YAP1 via the Hippo signaling pathway, and is associated with hyperandrogenism and abnormal steroidogenesis in PCOS [3,5]. In myeloid immune cells, ablation of Miga2 (Fam73b) switches mitochondrial morphology to fission, enhancing anti-tumor immunity [4].

In summary, MIGA2 is essential for lipid metabolism, autophagy, cell proliferation, and immune responses. Studies using gene-knockout models have revealed its role in diseases such as PCOS and in processes related to anti-tumor immunity. Understanding MIGA2 functions can provide insights into the mechanisms of these diseases and potentially lead to new therapeutic strategies.