Calcium and regulation of the mitochondrial permeability transition

• Published in: Cell calcium (Edinburgh) Vol. 70; pp. 56 - 63
• Main Authors: Giorgio, Valentina, Guo, Lishu, Bassot, Claudio, Petronilli, Valeria, Bernardi, Paolo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.03.2018
• Subjects: Animals; Ca2; Calcium - metabolism; Channels; F-ATP synthase; Humans; Mitochondria; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Proton-Translocating ATPases - metabolism; Models, Biological; Permeability transition; MMC; PT; PTP; Channels; CsA; PhAsO; Permeability transition; Mitochondria; F-ATP synthase; Ca2; Pi; CyP; BAPTA-AM; OH-PGO; Ca(2+)
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2017.05.004

[Display omitted] •Permeability transition pore (PTP) is a Ca2+-activated channel whose prolonged openings can lead to depolarization, Ca2+ release and cell death.•Our working hypothesis is that the channel forms from F-ATP synthase dimers following Ca2+-binding to the catalytic site.•Ca2+ competes with PTP-inhibitory Mg2+, and is an essential permissive factor for PTP opening.•Ca2+ binding could cause a conformational change transmitted via OSCP to the peripheral stalk and the the inner membrane. Recent years have seen renewed interest in the permeability transition pore, a high conductance channel responsible for permeabilization of the inner mitochondrial membrane, a process that leads to depolarization and Ca2+ release. Transient openings may be involved in physiological Ca2+ homeostasis while long-lasting openings may trigger and/or execute cell death. In this review we specifically focus (i) on the hypothesis that the PTP forms from the F-ATP synthase and (ii) on the mechanisms through which Ca2+ can reversibly switch this energy-conserving nanomachine into an energy-dissipating device.