Figure 5.
Potential mechanism for the involvement of mitoKATP in the proliferation of hPASMCs under hypoxic conditions. The mitochondrial inner membrane is polarized, with a negative matrix side due to a H+ gradient generated by respiratory enzyme complexes. ATP is generated from ADP by ATP synthase and the energy is stored as the ΔΨm. MitoKATP, which may be inhibited by ATP, mediates K+ influx along the ΔΨm, causing a decrease in ΔΨm and regulation of ROS generation. Due to dysfunction of respiratory chain complexes, ROS levels are upregulated by two positive feedback loops: ROS/HIF/miR-210/ISCU and ATP/mitoKATP/ΔΨm. Along with regulation of HIF-1α, the aberrant ROS levels lead to the proliferation of hPASMCs under hypoxic conditions. MitoKATP, mitochondrial ATP-sensitive potassium channel; hPASMCs, human pulmonary artery smooth muscle cells; ATP, adenoside triphosphate; ADP, adenoside diphosphate; ΔΨm, mitochondrial membrane potential; ROS, reactive oxygen species; HIF, hypoxia-inducible factor; miR, microRNA; ISCU, iron-sulfur cluster protein.