Organelle Contact Sites

Saverio Marchi, Mart Bittremieux, Sonia Missiroli, Claudia Morganti, Simone Patergnani, Luigi Sbano, Alessandro Rimessi, Martijn Kerkhofs, Jan B. Parys, Geert Bultynck, Carlotta Giorgi, Paolo Pinton, Marchi, Saverio, Bittremieux, Mart, Missiroli, Sonia, Morganti, Claudia, Patergnani, Simone, Sbano, Luigi, Rimessi, Alessandro, Kerkhofs, Martijn, Parys, Jan B., Bultynck, Geert, Giorgi, Carlotta, Pinton, Paolo

The execution of proper Ca(2+) signaling requires close apposition between the endoplasmic reticulum (ER) and mitochondria. Hence, Ca(2+) released from the ER is "quasi-synaptically" transferred to mitochondrial matrix, where Ca(2+) stimulates mitochondrial ATP synthesis by activating the tricarboxylic acid (TCA) cycle. However, when the Ca(2+) transfer is excessive and sustained, mitochondrial Ca(2+) overload induces apoptosis by opening the mitochondrial permeability transition pore. A large number of regulatory proteins reside at mitochondria-associated ER membranes (MAMs) to maintain the optimal distance between the organelles and to coordinate the functionality of both ER and mitochondrial Ca(2+) transporters or channels. In this chapter, we discuss the different pathways involved in the regulation of ER-mitochondria Ca(2+) flux and describe the activities of the various Ca(2+) players based on their primary intra-organelle localization.