TY - JOUR
T1 - PGRMC1
T2 - An enigmatic heme-binding protein
AU - McGuire, Meredith R.
AU - Espenshade, Peter J.
N1 - Funding Information:
We apologize to researchers whose studies were not discussed due to space limitations. We thank Deb Mukhopadhyay for assistance with CYB5 and PGRMC1 3D structure generation and structure alignment. This work was supported by the National Institutes of Health , grants HL077588 and GM126088 to P.J. Espenshade.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2023/1
Y1 - 2023/1
N2 - Progesterone Receptor Membrane Component 1 (PGRMC1) is a heme-binding protein that has been implicated in a wide range of cell and tissue functions, including cytochromes P450 activity, heme homeostasis, cancer, female reproduction, and protein quality control. Despite an extensive body of literature, a relative lack of mechanistic insight means that how PGRMC1 functions in these different aspects of biology is largely unknown. This review provides an overview of the PGRMC1 literature, highlighting what information is rigorously supported by experimental evidence and where additional investigation is warranted. The central role of PGRMC1 in supporting cytochrome P450 activity is discussed at length. Building on existing models of PGRMC1 function, a speculative model is proposed using the reviewed literature in which PGRMC1 functions as a heme chaperone to shuttle heme from its site of synthesis in the mitochondrion to other subcellular compartments. By spotlighting knowledge gaps, this review will motivate investigators to better understand this enigmatic protein.
AB - Progesterone Receptor Membrane Component 1 (PGRMC1) is a heme-binding protein that has been implicated in a wide range of cell and tissue functions, including cytochromes P450 activity, heme homeostasis, cancer, female reproduction, and protein quality control. Despite an extensive body of literature, a relative lack of mechanistic insight means that how PGRMC1 functions in these different aspects of biology is largely unknown. This review provides an overview of the PGRMC1 literature, highlighting what information is rigorously supported by experimental evidence and where additional investigation is warranted. The central role of PGRMC1 in supporting cytochrome P450 activity is discussed at length. Building on existing models of PGRMC1 function, a speculative model is proposed using the reviewed literature in which PGRMC1 functions as a heme chaperone to shuttle heme from its site of synthesis in the mitochondrion to other subcellular compartments. By spotlighting knowledge gaps, this review will motivate investigators to better understand this enigmatic protein.
KW - Chaperone
KW - Cytochrome P450
KW - Heme
KW - PGRMC1
KW - Progesterone
KW - cancer
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U2 - 10.1016/j.pharmthera.2022.108326
DO - 10.1016/j.pharmthera.2022.108326
M3 - Review article
C2 - 36463977
AN - SCOPUS:85143978865
SN - 0163-7258
VL - 241
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 108326
ER -