The IP3 receptor-mitochondria connection in apoptosis and autophagy

The amount of Ca2+ taken up in the mitochondrial matrix is a crucial determinant of cell fate; it plays a decisive role in the choice of the cell between life and death. The Ca2+ ions mainly originate from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores of the endoplasmic reticulum (ER). The uptake of these Ca2+ ions in the mitochondria depends on the functional properties and the subcellular localization of the IP3 receptor (IP3R) in discrete domains near the mitochondria. To allow for an efficient transfer of the Ca2+ ions from the ER to the mitochondria, structural interactions between IP(3)Rs and mitochondria are needed. This review will focus on the key proteins involved in these interactions, how they are regulated, and what are their physiological roles in apoptosis, necrosis and autophagy. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. (C) 2010 Elsevier B.V. All rights reserved.