Slc25a28, also known as MFRN2 (mitoferrin 2), is an iron transporter located in the inner mitochondrial membrane. It is crucial for mitochondrial iron homeostasis, which is involved in various biological processes such as electron transfer chain function, iron-sulfur cluster protein synthesis, and ferroptosis regulation [2,3,4,5,6].

In a study on adipose tissue, overexpression of Slc25a28 in C57BL/6J mice via adenovirus injection promoted lipid accumulation in white and brown adipose tissue, increased body weight, reduced serum triglyceride, and impaired serum glucose tolerance. It achieved this by reducing the protein expression of adipose TG lipase (ATGL) and inhibiting BAT formation [1]. In hepatic stellate cells, the BRD7-P53-Slc25a28 axis was found to play a crucial role in regulating ferroptosis. Mitochondrial p53 interacted with Slc25a28, enhancing its activity and leading to abnormal redox-active iron accumulation [2]. Microglial Slc25a28 deficiency in mice with intracerebral hemorrhage (ICH) ameliorated neuroinflammation, brain edema, and other injuries by restricting aerobic glycolysis. ICH stimulated mitochondrial iron overload and upregulated Slc25a28 expression [3].

In summary, Slc25a28 is essential for maintaining mitochondrial iron homeostasis and is involved in processes like adipogenesis, ferroptosis, and microglia activation after ICH. Mouse models with Slc25a28 overexpression or deficiency have revealed its role in these biological processes and associated disease conditions, highlighting its potential as a therapeutic target in obesity-related diseases, liver fibrosis, and ICH [1,2,3].