title: Physiological roles of the mitochondrial permeability transition pore.
abstract: Neurons experience high metabolic demand during such processes as synaptic vesicle recycling, membrane potential maintenance and Ca2+exchange/extrusion. The energy needs of these events are met in large part by mitochondrial production of ATP through the process of oxidative phosphorylation. The job of ATP production by the mitochondria is performed by the F1FOATP synthase, a multi-protein enzyme that contains a membrane-inserted portion, an extra-membranous enzymatic portion and an extensive regulatory complex. Although required for ATP production by mitochondria, recent findings have confirmed that the membrane-confined portion of 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, uncoupling of oxidative phosphorylation and cell death. Recent advances in understanding the molecular components of mPTP and its regulatory mechanisms have determined that decreased uncoupling occurs in states of enhanced mitochondrial efficiency; relative closure of mPTP therefore contributes to cellular functions as diverse as cardiac development and synaptic efficacy.
authors: Department Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA.
authors: Nelli
authors: N
authors: Mnatsakanyan
authors: Department of Pediatrics (Cardiology), University of Rochester Medical Center, Rochester, NY, USA.
authors: Gisela
authors: G
authors: Beutner
authors: Department of Pediatrics (Cardiology), University of Rochester Medical Center, Rochester, NY, USA.
authors: George A
authors: GA
authors: Porter
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Kambiz N
authors: KN
authors: Alavian
authors: Department Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA. elizabeth.jonas@yale.edu.
authors: Elizabeth A
authors: EA
authors: Jonas
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D016923:Cell Death; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010085:Oxidative Phosphorylation
chemical_list: D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases
keywords: ATP synthase; Mitochondria; Permeability transition pore; Synaptic plasticity; Synaptic transmission