Mitochondrial S-adenosylmethionine carrier protein (SLC25A26)

Mitochondrial S-adenosylmethionine carrier protein (SLC25A26) is a nuclear-encoded transporter localized in the mitochondrial inner membrane, responsible for importing S-adenosylmethionine (SAM) from the cytosol into mitochondria and exporting S-adenosylhomocysteine (SAH) in exchange. This process is essential for mitochondrial methylation reactions, which modify DNA, RNA, proteins, and amino acids, affecting mitochondrial gene expression, biosynthesis, and epigenetic regulation. Mutations in SLC25A26 lead to reduced mitochondrial methylation capacity, contributing to severe metabolic and mitochondrial diseases, and its dysregulation is implicated in several cancer types, influencing cell cycle progression, apoptosis, and chemosensitivity. Currently, cisplatin sensitivity is linked with SLC25A26 overexpression, but no targeted small-molecule drugs have been identified.

Other names

SLC25A26SAMCMitochondrial S-adenosylmethionine carrier proteinCOXPD28S-adenosylmethionine mitochondrial carrier proteinSolute carrier family 25 member 26Mitochondrial S-adenosylmethionine transporter

For cisplatin: Induction of apoptosis via enhanced mitochondrial SAM import, leading to cell cycle arrest, mtDNA hypermethylation, decreased ATP, and increased cytochrome c release. Speculatively, drugs targeting SAM/SAH transport or mitochondrial methylation may act via modulating methyl group availability and epigenetic state.