Organelles are mini-organs and carry out compartmentalized and specific functions inside cells. We are particularly focused on the endoplasmic reticulum and its metabolic biology and how it interacts and coordinates the function of other organelles such as mitochondria. Under this umbrella, we explore the requirements to maintain organelle integrity and function in two broad pillars. First, we investigate the molecular subcellular architecture of the cells, which we see as a new frontier in metabolic homeostasis and how theses structural changes relate to its function. Second, we explore organelle dysfunction and the generation of stress and inflammatory responses that set the stage for metabolic disease.