Reply To Bernardi: Themitochondrial Permeability Transition Pore And The Atp Synthase

The mitochondrial permeability transition pore (PTP) is a physiological phenomenon lacking a molecular basis. The phenomenon, described over 40 y ago, is that in response to elevated levels of Ca2+ ions in the mitochondrial matrix a nonspecific channel opens, water enters the mitochondria, their cristae swell, their membranes rupture, terminating ATP synthesis, and cell death by necrosis ensues (1). Pore opening can be inhibited by the binding of cyclosporin A to cyclophilin D, a prolyl cis–trans isomerase in the mitochondrial matrix that interacts with the pore without necessarily being a component. The open pore allows hydrophilic molecules up to a molecular weight of 1,500 Da to … [↵][1]1To whom correspondence may be addressed. Email: walker{at}mrc-mbu.cam.ac.uk. [1]: #xref-corresp-1-1