Mitochondria play important role in modulating metabolic responses of neutrophils during hypoxia. During hypoxic conditions, neutrophils synthesize enhanced mROS formation, which stabilizes HIF-1α, a transcriptional regulator that promotes oxygen delivery to hypoxic regions. This process relies on the G-3-P shuttle pathway. Modulation of glycolysis leading to increased flux through the G-3-P shuttle promotes enhanced mitochondrial membrane potential and mROS release during hypoxia. GPD2, the mitochondrial component of the G-3-P shuttle, is involved in promoting mROS synthesis, HIF-1α stabilization, and neutrophil survival during hypoxia. Professional illustration by Patrick Lane, ScEYEnce Studios.