title: The Mitochondrial Permeability Transition Pore and ATP Synthase.
abstract: Mitochondrial ATP generation by oxidative phosphorylation combines the stepwise oxidation by the electron transport chain (ETC) of the reducing equivalents NADH and FADH2with the generation of ATP by the ATP synthase. Recent studies show that the ATP synthase is not only essential for the generation of ATP but may also contribute to the formation of the mitochondrial permeability transition pore (PTP). We present a model, in which the PTP is located within the c-subunit ring in the Fosubunit of the ATP synthase. Opening of the PTP was long associated with uncoupling of the ETC and the initiation of programmed cell death. More recently, it was shown that PTP opening may serve a physiologic role: it can transiently open to regulate mitochondrial signaling in mature cells, and it is open in the embryonic mouse heart. This review will discuss how the ATP synthase paradoxically lies at the center of both ATP generation and cell death.
authors: Division of Cardiology, Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave., Box 631, Rochester, 14642, NY, USA.
authors: Gisela
authors: G
authors: Beutner
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Kambiz N
authors: KN
authors: Alavian
authors: Department of Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA.
authors: Elizabeth A
authors: EA
authors: Jonas
authors: Division of Cardiology, Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave., Box 631, Rochester, 14642, NY, USA. george_porter@urmc.rochester.edu.
authors: George A
authors: GA
authors: Porter
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D004579:Electron Transport; D004734:Energy Metabolism; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases / Q000502:physiology*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases
keywords: ATP synthase; Bioenergetics; Electron transport chain; Embryonic heart; Mitochondria; Permeability transition pore