Seminar

MCJ, a novel regulator of mitochondrial metabolism and cancer

Mercedes Rincón, PhD

An area of interest for Dr. Rincon is breast cancer and chemotherapy response. Her initial studies on the role of IL-6 in regulating breast cancer cell response to chemotherapy have been followed by studies on a novel molecule, MCJ/DnaJC15 cochaperone. Maintenance of mitochondrial membrane potential through the electron transfer chain (ETC) determines the rate of oxidative phosphorylation as a pathway for energy generation. Dr. Rincón has identified MCJ/DnaJC15 as a novel endogenous inhibitor of ETC complex I activity that serves to regulate cellular metabolism by slowing mitochondrial respiration. Hypermethylation-mediated transcriptional silencing of the MCJ gene has been associated with increased chemotherapeutic resistance in ovarian cancer. MCJ is expressed in drug-sensitive breast cancer cells but not in multidrug-resistant cells. The inhibition of MCJ expression increases resistance to specific drugs by inducing expression of the ABCB1 drug transporter that prevents intracellular drug accumulation. Thus, MCJ is required in these cells to maintain drug response. Dr. Rincon's studies in breast cancer go from in vitro molecular analysis, to in vivo mouse models of mammary cancer and human breast cancer patients. Dr. Rincon’s interests are not only on molecular mechanisms, but moving bench work to clinical translational research in the breast cancer area.