Slc25a39 is a mitochondrial membrane carrier. It is crucial for mitochondrial glutathione (GSH) import, a process essential for maintaining redox homeostasis in mitochondria [1,2,3]. As mitochondria are the major sites of oxidative reactions, GSH imported by Slc25a39 performs protective and biosynthetic functions. This process is also linked to iron metabolism and is involved in cell proliferation in vitro and red blood cell development in mice [1].

Loss-of-function studies, such as knocking out Slc25a39 in mammalian cells, have shown that its absence reduces mitochondrial GSH import and abundance without affecting cellular GSH levels [1]. Cells lacking both Slc25a39 and its paralogue Slc25a40 exhibit defects in the activity and stability of proteins containing iron-sulfur clusters [1]. In mice, Slc25a39 expression changes in response to conditions like bile duct ligation and lipopolysaccharide treatment, which are associated with changes in mitochondrial GSH levels [4]. In addition, in colorectal cancer, knockdown of Slc25a39 suppresses cell growth and migration while enhancing apoptosis, indicating its role in cancer progression [5].

In summary, Slc25a39 is essential for mitochondrial GSH import, which impacts multiple biological processes. Model-based research, especially gene knockout studies in mammalian cells and mice, has revealed its significance in redox homeostasis, iron metabolism, and disease-related processes such as cancer progression. Understanding Slc25a39 may offer new insights into treating conditions related to mitochondrial dysfunction and redox imbalance.