ABSTRACTTGF- affects virtually all aspects of mammalian physiology starting from early embryonic development to adulttissue homeostasis through regulation of diverse cellular functions including proliferation differentiation andapoptosis. TGF- signaling also plays an important role in cell metabolism although there has been incrementalprogress in understanding how it differentially regulates mitochondrial biogenesis respiration and organelledestruction. While such varying effects are theorized to occur primarily through slow-acting contextual generegulation TGF- is also capable of inducing more rapid direct and reversible changes in mitochondrial shapeand function through largely unknown mechanisms a key aspect that represents an important knowledge gapin the field. Our research program has focused on two powerfully opposing mechanisms by which two majorTGF- effectors Smad2 and TAK1 control mitochondrial fusion/fission dynamics to achieve and maintainmetabolic homeostasis. We seek to understand mechanisms governing their organization activation andregulation in mitochondrial remodeling and how they influence cell behavior using angiogenesis as adevelopmental model system. Our studies will provide unique perspectives on how the complex TGF- signalingnetworks control mitochondrial dynamics to affect their metabolic developmental and homeostatic roles invascular physiology.