The endoplasmic reticulum has a central role in biosynthesis of a variety of proteins and lipids. Mitochondria generate ATP, synthesize and process numerous metabolites, and are key regulators of cell death. The architectures of endoplasmic reticulum and mitochondria change continually via the process of membrane fusion, fission, elongation, degradation, and renewal. These structural changes correlate with important changes in organellar function. Both organelles are capable of moving along the cytoskeleton, thus changing their cellular distribution. Numerous studies have demonstrated coordination and communication between mitochondria and endoplasmic reticulum. A focal point for these interactions is a zone of close contact between them known as the mitochondrial-associated endoplasmic reticulum membrane (MAM), which serves as a signaling juncture that facilitates calcium and lipid transfer between organelles. Here we review the emerging data on how communication between endoplasmic reticulum and mitochondria can modulate organelle function and determine cellular fate. KeywordsCell death; endoplasmic reticulum; metabolism; mitochondria CONFLICT OF INTERESTThe authors confirm that this article content has no conflicts of interest. NIH Public Access Author ManuscriptCurr Mol Med. Author manuscript; available in PMC 2014 July 21. Published in final edited form as:Curr Mol Med. 2013 February ; 13(2): 317-329. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript ORGANELLE FUNCTIONThe endoplasmic reticulum (ER) is an organelle whose primary function is protein synthesis and folding [1]. One third of cellular proteins are synthesized by ER-associated ribosomes, particularly those destined for secretion [2]. In the ER lumen, nascent polypeptides are modified with N-linked glycans and made accessible to proteins involved in proper protein folding and quality control [3,4]. In addition, the ER is the main site for biosynthesis of a variety of lipids such as phospholipids, cholesterol, and ceramides, which are transported to other organelles and cellular membranes via vesicles of the secretory pathway [5].ER is composed of a series of continuous membranous structures that are organized into subdomains that include the rough ER, smooth ER, transitional ER and the nuclear envelope [6]. The architecture of the ER changes continually according to cellular demand through the processes of fusion, fission, elongation and membrane degradation [6]. Structural differences correlate with differences in ER function [6]. The rough ER is mainly laminal and associated with polyribosomes for protein synthesis. The smooth ER is primarily composed of tubular structures. This is the site of phospholipid biosynthesis and is the chief point of contact with other organelles [6]. Changes in ER membrane curvature and structure are facilitated by several proteins, including GTPases and reticulons [6]. For a detailed view of ER structure and related processes, readers are referred to a recent excellent review by Park ...