Sensory neurons respond to hypoxia with NO production associated with mitochondria

Oxygen is pivotal for mammalian cell function, and recent studies suggest an involvement of NO in cellular adaptation to low oxygen supply. Here, we report that endothelial NO-synthase is ubiquitously expressed in rat and mice sensory neurons, and is targeted to juxtamitochondrial compartments of the ER. There it is activated in response to hypoxia while generation of reactive oxygen species remains unaltered. Developing a technique for ultrastructural localization of an NO-sensitive indicator allowed to identify the inner mitochondrial membrane as the target of NO under hypoxia. The demonstrated hypoxic stimulation of endothelial NOS in sensory neurons shall contribute to resistance against hypoxia, since NO promotes cellular survival by interfering with mitochondrial function.