The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor β signaling

ABSTRACT Neuronal regeneration is a highly energy‐demanding process that greatly relies on axonal mitochondrial transport to meet the enhanced metabolic requirements. Mature neurons typically fail to regenerate after injury, partly because of mitochondrial motility and energy deficits in injured axons. Retinoic acid receptor (RAR)‐β signaling is involved in axonal and neurite regeneration. Here we investigate the effect of RAR‐β signaling on mitochondrial trafficking during neurite outgrowth and find that it enhances their proliferation, speed, and movement toward the growing end of the neuron via hypoxia‐inducible factor 1α signaling. We also show that RAR‐β signaling promotes the binding of the mitochondria to the anchoring protein, glucose‐related protein 75, at the growing tip of neurite, thus allowing them to provide energy and metabolic roles required for neurite outgrowth.—Trigo, D., Goncalves, M. B., Corcoran, J. P. T. The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor β signaling. FASEB J. 33, 7225–7235 (2019). www.fasebj.org