Mitochondrial folate transport becomes essential in serine/glycine-starved triple-negative breast cancer

Loss of the mitochondrial folate transporter SLC25A32 sensitizes murine and human triple-negative breast cancer cells to glycine starvation, suppressing tumor growth under dietary serine/glycine restriction.

• Why it matters: Triple-negative breast cancers often upregulate serine synthesis, making them resistant to exogenous serine/glycine restriction, so new vulnerabilities under nutrient limitation are needed.
• What they did: A metabolic CRISPR dropout screen in serine/glycine–resistant TNBC cells identified mitochondrial folate metabolism as a critical dependency, with SLC25A32 loss tested in murine and human cancer models.
• The result: SLC25A32 deficiency disrupts folate-dependent glycine production, causing glycine auxotrophy, glutathione depletion, and oxidative stress, and it impairs metastatic potential.