Summary Mitochondria are endosymbiotic organelles and have retained a reduced genome packaged into 100-1000 copies of nucleoids per cell, distributed within dynamic mitochondria “syncytia”. Mitochondria are the metabolic hubs of eukaryotic cells, producing ATP via oxidative phosphorylation and other critical building blocks. They have evolved to behave dynamically and to be an integrating platform for the assembly and regulation of signaling pathways, such as cell death and innate immunity. Given their central roles, it is not surprising that that mitochondrial dysfunction is associated with an increasingly large proportion of human inherited disorders and with common diseases, such as neurodegenerative disorders, metabolic syndromes, and cancer. To gain insight into the roles of mitochondria in sickness and in health, we are focused on how mitochondrial behavior is controlled within cells and how this behavior is intertwined with metabolism and cell behavior. Our current research addresses the outstanding questions of how mitochondrial DNA copy number and transmission is controlled in cells, how the mitochondrial inner membrane is differentiated into distinct domains and how mitochondrial behavior, metabolism and cell behavior are integrated. Addressing these questions will illuminate how mitochondria contribute to cellular homeostasis and pathogenesis.