LAUSR

Whether the mitochondrial permeability transition pore (PTP), also called mitochondrial megachannel (MMC), originates from the F‐ATP synthase is a matter of controversy. This hypothesis is supported both by site‐directed mutagenesis of specific residues of F‐ATP synthase affecting regulation of the PTP/MMC and by deletion of specific subunits causing dramatic changes in channel conductance. In contrast, human cells lacking an assembled F‐ATP synthase apparently display persistence of the PTP. We discuss recent data that shed new light on this controversy, supporting the conclusion that the PTP/MMC originates from a Ca2+‐dependent conformational change in F‐ATP synthase allowing its reversible transformation into a high‐conductance channel.