The mitochondrial permeability transition pore and its adaptive responses in tumor cells

This review covers recent progress on the nature of the mitochondrial permeability transition pore (PTP) - a key effector in the mitochondrial pathways to cell death - and on the adaptive responses of tumor cells that desensitize the PTP to Ca2+ and reactive oxygen species (ROS), thereby playing an important role in the resistance of tumors to cell death. The discovery that the PTP forms from dimers of F-ATP synthase; and the definition of the Ca2+- and ROS-dependent signaling pathways affecting the transition of the F-ATP synthase from an energy-conserving to an energy-dissipating device open new perspectives for therapeutic intervention in cancer cells. (C) 2014 The Authors. Published by Elsevier Ltd.