Imaging mitochondrial signaling in beta cells (? cells) ectopically implanted in the eye. In the last 20 years, it became clear that defects in the mitochondrial energy producing system, either genetic or toxin-induced, cause many different phenotypes. Therefore, defects in one of the five mitochondrial oxidative phosphorylation (OXPHOS) complexes likely trigger distinct signaling pathways, which differentially affect specific cell types. This team will use mouse models with specific defects in complexes I, III or IV to explore enzyme-specific signaling events in mitochondrial disorders. A novel model will be used to test this hypothesis in a dynamic, real-time platform. The approach will involve implanting ? cells in the anterior chamber of the mouse eye, which allows for the use of imaging techniques to follow both cellular and mitochondrial function as well as its signaling patterns in vascularized environment akin to the in vivo situation. This is a multiple Principal Investigator application that will use the expertise of the group of Dr. Alejandro Caicedo (?-cell implant model, imaging physiological biomarkers) and the group of Dr. Carlos Moraes (mitochondrial physiology and mouse models of OXPHOS defects) to tease out signaling signatures associated with defects (genetic or toxin-induced) in specific OXPHOS complexes.
This research team will use the expertise of two groups to develop an in vivo system to study mitochondrial signaling associated with mitochondrial OXPHOS defects. ? cells with genetic or toxin-induced defects in different OXPHOS complexes will be implanted in the anterior chamber of a recipient mouse, which will provide a transparent window to image signaling sensors.
