Global and mitochondrial proteomics under GSH depletion

Glutathione (GSH) is a tripeptide thiol abundantly present in all eukaryotes1. As the major site of oxidative metabolism, mitochondria must maintain sufficient levels of GSH in order to perform key protective and biosynthetic functions. GSH is exclusively synthesized in the cytosol, yet how it enters mitochondria and the molecular machinery involved in mitochondrial GSH import remain elusive. Here, using mass-spectrometry approaches, we identify SLC25A39, a mitochondrial membrane carrier of unknown function, to mediate GSH transport into mitochondria. SLC25A39 loss reduces mitochondrial GSH import and abundance, without impacting whole cell GSH levels.