OrgaNet · From Isolated Compartments to Intracellular Networks: Deciphering Interorganelle Communication

Organelles exchange metabolites and information to coordinate essential aspects of cellular physiology, thus behaving as an integrated intracellular network. For example, the endoplasmic reticulum (ER) makes contacts with several organelles, including the plasma membrane, mitochondria, the Golgi apparatus, and lysosomes. These contacts allow the coordination of calcium and lipid homeostasis across the cell. Yet, little is known about their molecular nature. A long-standing question in cell biology has been how membrane-rich mitochondria receive lipids synthesized in the ER in the absence of vesicular transport between the two organelles. One model suggests that lipids directly shuttle from one organelle to the other at sites of contact, although the hypothesis lacked molecular details.A breakthrough in the field resulted from my postdoctoral research in Peter Walter's laboratory, where I discovered a protein complex that tethers the ER and the mitochondria. This tethering complex called ER-Mitochondria Encounter Structures (ERMES) provides the tethering force necessary to physically couple the two organelles. Our discovery of molecular components of ER-mitochondria junctions opened a fascinating new area of research in interorganelle communication. Our long-term goals for ER-mitochondria study are to understand: (a) the physiological importance of these connections, how they facilitate interorganelle metabolite transport and how this transport affects the functionality of the respective organelles, (b) the molecular architecture that results in interorganelle tethering, (c) the regulation of these junctions, and (d) the conservation between yeast and higher eukaryotes.As most membrane bound compartments establish networks of contact sites with their neighbors, we anticipate that the findings of our proposed ERC research on the ERMES complex will set a framework for deciphering the entire intracellular interorganelle network.