ABSTRACT
The identification of the molecular composition of the mitochondrial calcium uniporter has allowed for the genetic manipulation of its components and the creation of various in vivo genetic models. Here, we review the initial attempts to modulate the expression of components of the calcium uniporter in a range of organisms from plants to mammals. This analysis has confirmed the strict requirement for the uniporter for in vivo mitochondrial calcium uptake and for maintaining mitochondrial calcium homeostasis. We further discuss the physiological effects following genetic manipulation of the uniporter on tissue bioenergetics and the threshold for cell death. Finally, we analyze the limited information regarding the role of various uniporter components in human disease.