HMGB1 increases Drp1 phosphorylation and Drp1‐dependent mitochondrial fission through activation of ERK1/2 signaling pathway, and subsequently stimulates autophagy activation, which further lead to BMPR2 lysosomal degradation and Id1 downregulation, and ultimately promotes PASMCs proliferation/migration and pulmonary vascular remodeling in PAH. This evidence concerns the gene HMGB1 and pulmonary arterial hypertension.