The subcellular distribution of mitochondria may influence cellular functions by controlling the local levels of second messengers including reactive oxygen species (ROS). Al-Mehdi et al. describe how perinuclear clustering of mitochondria can regulate hypoxia-induced gene expression. Hypoxia was found to trigger microtubule-dependent accumulation of mitochondria near the nucleus in pulmonary artery endothelial cells. This correlated with high nuclear ROS levels and oxidative modifications at the VEGF (vascular endothelial growth factor) promoter. The resulting increase in binding of hypoxia-induced factor 1α (HIF1α) to the VEGF promoter and in VEGF mRNA levels suggested that mitochondrial localization can regulate hypoxia-induced gene expression.