title: From ATP to PTP and Back: A Dual Function for the Mitochondrial ATP Synthase.
abstract: Mitochondria not only play a fundamental role in heart physiology but are also key effectors of dysfunction and death. This dual role assumes a new meaning after recent advances on the nature and regulation of the permeability transition pore, an inner membrane channel whose opening requires matrix Ca(2+) and is modulated by many effectors including reactive oxygen species, matrix cyclophilin D, Pi (inorganic phosphate), and matrix pH. The recent demonstration that the F-ATP synthase can reversibly undergo a Ca(2+)-dependent transition to form a channel that mediates the permeability transition opens new perspectives to the field. These findings demand a reassessment of the modifications of F-ATP synthase that take place in the heart under pathological conditions and of their potential role in determining the transition of F-ATP synthase from and energy-conserving into an energy-dissipating device.
authors.affiliation: From the Department of Biomedical Sciences, University of Padova, Italy (P.B., F.D.L.); and Department of Medical and Biological Sciences (F.F) and Department of Food Science (G.L.), University of Udine, Udine, Italy. bernardi@bio.unipd.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.affiliation: From the Department of Biomedical Sciences, University of Padova, Italy (P.B., F.D.L.); and Department of Medical and Biological Sciences (F.F) and Department of Food Science (G.L.), University of Udine, Udine, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.affiliation: From the Department of Biomedical Sciences, University of Padova, Italy (P.B., F.D.L.); and Department of Medical and Biological Sciences (F.F) and Department of Food Science (G.L.), University of Udine, Udine, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.affiliation: From the Department of Biomedical Sciences, University of Padova, Italy (P.B., F.D.L.); and Department of Medical and Biological Sciences (F.F) and Department of Food Science (G.L.), University of Udine, Udine, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lippe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010539:Permeability
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases; D002118:Calcium
keywords: Ca(2+)-Mg(2+)-ATPase; mitochondria; permeability transition pore