title: Cell death disguised: The mitochondrial permeability transition pore as the c-subunit of the F(1)F(O) ATP synthase.
abstract: Ion transport across the mitochondrial inner and outer membranes is central to mitochondrial function, including regulation of oxidative phosphorylation and cell death. Although essential for ATP production by mitochondria, recent findings have confirmed that the c-subunit of the ATP synthase also houses a large conductance uncoupling channel, the mitochondrial permeability transition pore (mPTP), the persistent opening of which produces osmotic dysregulation of the inner mitochondrial membrane and cell death. This review will discuss recent advances in understanding the molecular components of mPTP, its regulatory mechanisms and how these contribute directly to its physiological as well as pathological roles.
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA. Electronic address: Elizabeth.jonas@yale.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jonas
authors.affiliation: Department of Pediatrics (Cardiology), University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Porter
authors.affiliation: Department of Pediatrics (Cardiology), University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Gisela
authors.initials: G
authors.lastname: Beutner
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA.
authors.forename: Nelli
authors.initials: N
authors.lastname: Mnatsakanyan
authors.affiliation: Division of Brain Sciences, Department of Medicine, Imperial College London, UK.
authors.forename: Kambiz N
authors.initials: KN
authors.lastname: Alavian
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D016923:Cell Death / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases
keywords: Calcium dysregulation; Cell death; Ion channels; Metabolism; Mitochondria