Oxygen-dependent regulation of serotonin receptor 5-HT in hypoxic response and flight performance in bumblebees, Bombus terrestris

Bumblebees, as indispensable pollinators, possess energy-intensive flight that depends on efficient oxygen and energy utilization. However, how aerobic and anaerobic metabolisms in flight muscles are coordinated under varying oxygen levels remains unresolved. Here, we identify the serotonin receptor <i>5-HT</i> _<i>1A</i> as a potential oxygen-responsive factor in the flight muscles of <i>Bombus terrestris</i>. Under oxygen-limited conditions (1.6-12 kPa), bumblebees significantly reduced thoracic temperature, respiration, and flight performance and even induced stupor, accompanied by mitochondrial damage in the flight muscles. Transcriptomic analysis under hypoxic conditions revealed 711 differentially expressed genes enriched in G-protein-coupled receptors and energy metabolism pathways. Notably, <i>5-HT</i> _<i>1A</i> expression was upregulated by hypoxia and downregulated by flight activity. Antagonist inhibition of <i>5-HT</i> _<i>1A</i> enhanced flight speed, duration, and distance under both normoxic and hypoxic conditions. Together, these findings suggest that <i>5-HT</i> _<i>1A</i> may mediate oxygen-dependent regulation of flight performance, potentially acting as a negative modulator.