Mitochondria are highly dynamic organelles that continuously move, divide and fuse in a highly regulated fashion. The balance between the opposing processes of mitochondrial fusion and fission is controlled by a growing family of “mitochondria-shaping” proteins. Evidence is accumulating on the role of these proteins in several functions, from apoptosis to Ca2+ signaling, to morphogenesis of dendritic spines and synapses, to regulation of migration of leukocytes. The knowledge of the regulation of mitochondrial dynamics, as well as its impact on tissue development and homeostasis is currently limited. This project hypothesizes that changes in mitochondrial morphology are crucial events in determining migration and development of T cells in the thymus. We will capitalize on the mouse models available in the host laboratory to (i) address whether mitochondrial dynamics regulates motility of lymphocytes in intact mouse thymic lobes; (ii) understand whether pro-fusion or pro-fission proteins regulate T cell development; (iii) dissect the role of fusion vs. antiapoptotic effect of pro-fusion protein in T cell migration and development. Our project is expected to clarify the role of mitochondrial dynamics in a complex immunological scenario like thymic development.
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