Thoughts on interactions between PGRMC1 and diverse attested and potential hydrophobic ligands

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Progesterone Receptor Membrane Component 1 (PGRMC1) has diverse subcellular locations and functions.
• PGRMC1 interacts with ferrochelatase in the mitochondrial outer membrane, the final step in heme synthesis.
• PGRMC1 is proposed to chaperone heme to cytochrome P450 (cyP450) enzymes.

Purpose of the Study:

• To explore PGRMC1's roles in transferring heme and hydrophobic ligands like cholesterol and steroids.
• To review heme synthesis, cholesterol transport, and PGRMC1's involvement in cholesterol regulation and pregnenolone production.
• To propose novel hypothetical models for PGRMC1 function.

Main Methods:

• Literature review on PGRMC1, heme, cholesterol, and cyP450 enzymes.
• Clustering by Inferred Models of Evolution (CLIME) analysis to assess protein co-evolution.
• Analysis of PGRMC1's evolutionary relationship with cyP450 enzymes and mitochondrial proteins.

Main Results:

• PGRMC1 interacts with ferrochelatase and may shuttle heme.
• PGRMC1 is involved in cholesterol regulation and pregnenolone production.
• CLIME analysis reveals co-evolution of PGRMC1 with cyP450 enzymes and certain mitochondrial proteins, with some being dispensable in parasitic protists.

Conclusions:

• PGRMC1 plays significant roles in sterol synthesis and energy regulation.
• PGRMC1's functions appear dispensable in certain parasitic organisms.
• Novel functional models for PGRMC1 are proposed for future research.