title: Changes in the mitochondrial permeability transition pore in aging and age-associated diseases.
abstract: Aging is a biological process associated with impairment of mitochondrial bioenergetic function, increased oxidative stress, attenuated ability to respond to stresses and increased risk in contracting age-associated diseases. When mitochondria are subjected to oxidative stress, accompanied by calcium overload and ATP depletion, they undergo "a permeability transition", characterized by sudden induced change of the inner mitochondrial membrane permeability for water as well as for low-molecular weight solutes (≤1.5kDa), resulting in membrane depolarization and uncoupling of oxidative phosphorylation. Research interest in the entity responsible for this phenomenon, the "mitochondrial permeability transition pore" (MPTP) has dramatically increased after demonstration that it plays a key role in the life and death decision in cells. The molecular structure and identity of MPTP is not yet known, although the pore is thought to exist as multiprotein complex. Some evidence indicate that the sensitivity of mitochondria to Ca(2+)-induced MPTP opening increases with aging; however the basis of this difference is unknown. Changes in MPTP structure and/or function may have important implications in the aging process and aged-associated diseases. This article examines data relevant to this issue. The important role of a principal lipidic counter-partner of the MPTP, cardiolipin, will also be discussed.
authors.affiliation: Department of Biosciences Biotechnologies and Biopharmaceutical, University of Bari and Institute of Biomembranes and Bioenergetics, National Research Council of Italy, Bari, Italy. g.paradies@biologia.uniba.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paradies
authors.forename: Valeria
authors.initials: V
authors.lastname: Paradies
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Ruggiero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Petrosillo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D000083162:Mitochondrial Permeability Transition Pore; D046912:Multiprotein Complexes / Q000378:metabolism*; D018384:Oxidative Stress; D010539:Permeability
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D046912:Multiprotein Complexes; D000255:Adenosine Triphosphate