Reprint of “The mitochondrial permeability transition pore and its adaptive responses in tumor cells”

• The mitochondrial permeability transition pore (PTP) is a key effector in the pathways to cell death.
• The PTP forms from F-ATP synthase and is regulated by several signaling pathways.
• Tumor cells desensitize the PTP to Ca2+ and reactive oxygen species increasing their resistance to death.
• The PTP is a target for anticancer chemotherapeutics.

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.

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