THE PERMEABILITY TRANSITION PORE AS A MITOCHONDRIAL CALCIUM-RELEASE CHANNEL - A CRITICAL-APPRAISAL

Mitochondria from a variety of sources possess an inner membrane chann el, the permeability transition pore. The pore is a voltage-dependent channel, activated by matrix Ca2+ and inhibited by matrix H+, which ca n be blocked by cyclosporin A, presumably after binding to mitochondri al cyclophilin. The physiological function of the permeability transit ion pore remains unknown. Here we evaluate its potential role as a fas t Ca2+ release channel involved in mitochondrial and cellular Ca2+ hom eostasis. We (i) discuss the theoretical and experimental reasons why mitochondria need a fast, inducible Ca2+ release channel; (ii) analyze the striking analogies between the mitochondrial permeability transit ion pore and the sarcoplasmic reticulum ryanodine receptor-Ca2+ releas e channel; (iii) argue that the permeability transition pore can act a s a selective release channel for Ca2+ despite its apparent lack of se lectivity for the transported species in vitro; and (iv) discuss the i mportance of mitochondria in cellular Ca2+ homeostasis, and how disrup tion of this function could impinge upon cell viability, particularly under conditions of oxidative stress.