Mitochondria position and function play instructive roles in presynaptic release properties and axon morphogenesis

My laboratory is focusing on the cellular, molecular and evolutionary mechanisms underlying the establishment of cortical connectivity. I will present recent published and unpublished results uncovering a new signaling pathway regulating terminal axon branching and presynaptic function through the regulation of mitochondria position, structure and function. Our results demonstrate that (1) the presynaptic capture of mitochondria plays a critical role during terminal axon branching, (2) presynaptic mitochondria play a critical role in regulating presynaptic calcium homeostasis thereby ditacting bouton-specific neurotransmitter release properties, (3) that mitochondria fission is dominant in axons (whereas mitochondria fusion is dominant in dendrites) and that the main factor promoting mitochondria fission in axons is Mff, one of four Drp1 receptors. Mff-loss-of-function results in significant longer mitochondria that are still successfully captured presynaptically but aberrantly uptake too much calcium resulting in decreased cytoplasmic calcium accumulation during neurotransmission. Finally, I will show that these novel signaling pathways we recently identified as critical regulators of mitochondria morphology and function underlie the loss of synapses characterizing the early stages of Alzheimer’s disease.