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Structure and physiological role of the mitochondrial permeability transition pore
Eliáš, Jan ; Mráček, Tomáš (advisor) ; Kalous, Martin (referee)
Mitochondrial permeability transition pore (mPTP) is Ca2+ dependent channel localised in the inner mitochondrial membrane. One of its defining characteristics is inhibition by nanomolar concentrations of immunosuppressant cyclosporine A (CsA). Together with additional interacting proteins, which regulate its opening, mPTP forms a permeability transition protein complex. Persistent opening of mPTP is accompanied by mitochondrial swelling and a subsequent collapse of organelle, which precedes release of proapoptotic proteins and programmed cell death. Channel forming unit of mPTP remains unknown, despite intense and long-lasting study. Numerous proteins were proposed to play a role of channel forming subunit of mPTP, including complex of ANT and VDAC, ANT alone, PiC or even ATP synthase. Despite the fact, that molecular structure remains elusive, mPTP seems to play a role in a range of pathophysiological processes or diseases associated with them. Among others this includes ischemia/reperfusion injury, neurological and muscle dystrophies, or tumorigenesis. Keywords: mitochondria, mitochondrial permeability transition pore, cyclosporine A, programmed cell death, ATP synthase, oxidative phosphorylation apparatus.
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