Dysfunctional Mitochondria and Hemolysis are Linked by Impaired Maturation of Reticulocytes: Possible Role in Pulmonary Hypertension.

We show that mitochondrial dysfunction impaired reticulocyte maturation promotes hemolysis resulting in increased CFH. Elevated CFH can trigger pathogenic pathways leading to PH/PAH via EC barrier dysfunction and increased PASMC proliferation. Treatment approaches that improve mitochondrial metabolism (LA) or inhibit free heme entrance to the cell (SL) abrogate the PH phenotype, highlighting the critical role of free heme-induced signaling in disease pathobiology.