TRPML1 loss disrupts lysosome–mitochondria homeostasis and sensitizes MDA-MB-231 triple-negative breast cancer cells to chemotherapy

responses, broad metabolic remodelling, G0/G1 arrest, and caspase-3/7-independent cell death. Importantly, ML1-KD cells showed enhanced responses to otherwise subeffective concentrations of doxorubicin and paclitaxel. Together, our findings support TRPML1-dependent lysosomal signaling as an important contributor to mitochondrial-metabolic resilience and chemotherapy responsiveness in MDA-MB-231 TNBC cells.