Dysfunctional mitochondria contribute to the onset of malignant transformation and growth. Molecules that regulate mitochondrial homeostasis are therefore the object of great attention to identify novel therapeutic strategies. The mitochondrial translocator protein (mTSPO) stands in a critical position for mitochondrial homeostasis and is involved in the physiology of breast cancer where it is overexpressed and positively associated with aggressiveness . mTSPO ligands are therefore exploited for cancer imaging and chemotherapy, such as PK11195. mTSPO is associated with the voltage-dependent anion channels (VDACs), which regulate the metabolites' flux into mitochondria . mTSPO expression is driven by the oncogene protein kinase Cε, suggesting a fundamental crosstalk for malignant transformation and uncontrolled proliferation. We hypothesized that mTSPO by regulating VDAC performance impinges on metabolism and pharmacologically induced cell death in breast cancer cells.