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.