The permeability transition pore as a mitochondrial calcium release channel: a critical appraisal.
Mitochondria from a variety of sources possess an inner membrane channel, the permeability transition pore. The pore is a voltage-dependent channel, activated by matrix Ca2+ and inhibited by matrix H+, which can be blocked by cyclosporin A, presumably after binding to mitochondrial cyclophilin. The physiological function of the permeability transition pore remains unknown. Here we evaluate its potential role as a fast Ca2+ release channel involved in mitochondrial and cellular Ca2+ homeostasis. 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 transition pore and the sarcoplasmic reticulum ryanodine receptor-Ca2+ release channel; (iii) argue that the permeability transition pore can act as a selective release channel for Ca2+ despite its apparent lack of selectivity for the transported species in vitro; and (iv) discuss the importance of mitochondria in cellular Ca2+ homeostasis, and how disruption of this function could impinge upon cell viability, particularly under conditions of oxidative stress.
Bernardi
P
P
CNR Unit for the Study of Biomembranes, Department of Biomedical Sciences, University of Padova, Italy.
Petronilli
V
V
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D017136:Ion Transport; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D010539:Permeability; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels