A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase

• DOI: 10.1021/acs.biochem.6b00756
• Publication Date: 2016-09-06T14:28:57Z
• Authors: Robert B. Piel; Mesafint T. Shiferaw; Ajay A. Vashisht; Jason R. Marcero; Jeremy L. Praissman; John D. Phillips; James A. Wohlschl...; Amy E. Medlock
• Keywords: Ferrochelatase; Progesterone receptor

Heme is an iron-containing cofactor essential for multiple cellular processes and fundamental activities such as oxygen transport. To better understand the means by which heme synthesis regulated during erythropoiesis, affinity purification coupled with mass spectrometry (MS) was performed to identify putative protein partners interacting ferrochelatase (FECH), terminal enzyme in biosynthetic pathway. Both progesterone receptor membrane component 1 (PGRMC1) 2 (PGRMC2) were identified these experiments. These interactions validated reciprocal followed MS analysis immunoblotting. The interaction between PGRMC1 FECH confirmed vitro HEK 293T cells, a non-erythroid cell line. When cells that are recognized models erythroid differentiation treated small molecule inhibitor of PGRMC1, AG-205, there observed decrease level hemoglobinization relative untreated cells. In transfer experiments showed purified able donate apo-cytochrome b5. presence measured activity decreased dose-dependent manner. Interactions strongest conformation associated product release, suggesting may regulate controlling release. Overall, data illustrate role regulating via suggest be chaperone or sensor.