ER-to-mitochondria miscommunication and metabolic diseases

Abstract

Eukaryotic cells contain a variety of subcellular organelles, each of which performs unique tasks. Thus follows that in order to coordinate these different intracellular functions, a highly dynamic system of communication must exist between the various compartments. Direct endoplasmic reticulum (ER)–mitochondria communication is facilitated by the physical interaction of their membranes in dedicated structural domains known as mitochondria-associatedmembranes (MAMs),which facilitate calcium(Ca2+) and lipid transfer between organelles and also act as platforms for signaling. Numerous studies have demonstrated the importance ofMAMin ensuring correct function of both organelles, and recently MAMs have been implicated in the genesis of various human diseases. Here, we review the salient structural features of interorganellar communication via MAM and discuss themost common experimental techniques employed to assess functionality of these domains. Finally, we will highlight the contribution of MAM to a variety of cellular functions and consider the potential role of MAMin the genesis ofmetabolic diseases. In doing so, the importance for cell functions of maintaining appropriate communication between ER and mitochondria will be emphasized.