New Roles for an Old Pore.

Biological organisms depend on a variety of mechanisms to remove defective components. Such was originally thought to be the function of the mitochondrial permeability transition, in which high-conductance permeability transition pores (PTP) form in the inner mitochondrial membrane, causing immediate matrix depolarization, Ca release, reversal of ATP synthase, matrix swelling, and eventually rupture of the outer mitochondrial membrane, releasing proapoptotic signaling molecules, such as cytochrome c (Figure). PTP formation is triggered primarily by reactive oxygen species (ROS) and matrix Ca overload. Originally interpreted as a suicide switch to remove defective mitochondria spewing excess ROS, PTP were later discovered to open transiently in a lower conductance mode hypothesized to serve a useful physiological role—namely as a mechanism to allow Ca-overloaded mitochondria to flush Ca from the matrix.