Solute carrier family 25 member 28 (SLC25A28)

Solute carrier family 25 member 28 (SLC25A28), also known as mitoferrin-2, is a mitochondrial transmembrane protein that functions as an iron transporter, mediating the import of ferrous iron into the mitochondrial matrix[1][3]. This process is necessary for the synthesis of iron-sulfur clusters and heme, which are critical for multiple mitochondrial and cellular enzymatic functions. SLC25A28 is expressed in many tissues and acts redundantly with its paralog, SLC25A37 (mitoferrin-1), with specialization in non-erythroid cells. In cancer biology, it is a synthetic lethal target in tumors with chromosome 8p deletions and impaired SLC25A37 expression, where its inhibition leads to severe mitochondrial dysfunction and cell death, representing a precision oncology opportunity[1]. SLC25A28 also plays a role in mitochondrial iron homeostasis outside of cancer settings, including in rare anemia syndromes and hepatic iron-induced apoptosis[3][4].

Other names

Mitoferrin-2MFRN2NPD016MRS3/4MRS4LMitochondrial RNA-splicing protein 3/4 homologMitochondrial iron transporter 2Putative mitochondrial solute carrier

Synthetic lethality in 8p-deleted cancers: Targeting SLC25A28 in cells lacking its paralog (SLC25A37/MFRN1) induces mitochondrial dysfunction, iron-sulfur cluster depletion, impaired respiration, DNA damage, and cell death[1]. Modulation of iron-induced apoptosis in hepatic cells through interactions with p53[4].