title: Mitochondrial contact sites: their role in energy metabolism and apoptosis.
abstract: The energy metabolism of the failing heart is characterised by a 30% decrease of the total adenine nucleotides content and what may be more important by a 60% loss of creatine and creatine phosphate [J.S. Ingwall, R.G. Weiss, Is the failing heart energy starved? On using chemical energy to support cardiac function, Circ. Res. 95 (2004) 35-145]. Besides the effect of these changes on the energy supply, failing heart is known to be more vulnerable to Ca2+ overload and apoptosis-inducing processes. Recent studies have pointed to the critical role of mitochondrial contact sites in controlling both the mitochondrial energy metabolism and Ca2+ homeostasis. This review focuses on the structure and function of protein complexes in mitochondrial contact sites and their regulatory role in the cellular bioenergetics, intra- and extra-mitochondrial Ca2+ levels, and release of apoptosis-inducing factors. Firstly, we review the compositions of different contact sites following by the discussion of experimental data obtained with isolated and reconstituted voltage-dependent anion channel-adenine nucleotide translocase complexes and consequences of the complex disassembling. Furthermore, we describe experiments involving the complex-stabilizing conditions in vitro and in intact cells. At the end, we discuss unsolved problems and opportunities for clinical application of the complex-stabilizing factors.
authors.affiliation: Department of Pharmacology and Physiology, Box 711, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA. dieter.brdiczka@uni-konstanz.de
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Brdiczka
authors.forename: Dmitry B
authors.initials: DB
authors.lastname: Zorov
authors.forename: Shey-Shing
authors.initials: SS
authors.lastname: Sheu
mesh_terms: D000818:Animals; D017209:Apoptosis; D045304:Cytochromes c / Q000378:metabolism; D004734:Energy Metabolism; D008928:Mitochondria / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism
chemical_list: D045304:Cytochromes c; D000226:Mitochondrial ADP, ATP Translocases