Longevity & AgingMitochondrial Glutathione Fuels Breast Cancer Spread to the Lung
Researchers discovered that breast cancer cells accumulating mitochondrial glutathione (GSH) via the transporter SLC25A39 gain a critical advantage during lung metastasis. Using mitochondrial metabolomics, genetic screens, and patient-derived models, they showed that SLC25A39 loss blocks metastatic colonization without affecting primary tumor growth. Conversely, boosting mitochondrial GSH accelerated metastasis. The mechanism involves ATF4, a stress-response transcription factor: SLC25A39 is required for optimal ATF4 activation under hypoxia and stress, linking mitochondrial GSH availability to adaptive signaling during early colonization. These findings position mitochondrial GSH as a limiting, druggable metabolite in metastatic breast cancer.
