Fig. 8.

Proposed mechanism for the role of AIF in PASMC proliferation. AIF was ubiquitylated in PASMCs by interacting with UBA52 under hypoxic conditions. On the one hand, in mitochondria, the transfer of AIF to the electron transport chain is reduced, which leading to OXPHOS defects and exacerbated ROS generation-induced mitophagy and autophagy. On the other hand, in the cytoplasm, mitochondrial dysfunction together with the degradation of AIF resulted in the increased expression of HK II and PKM2 and glycolysis activation. Finally, autophagy and glycolysis regulated by AIF induce the proliferation of PASMCs