ArticleThe Journal of biological chemistry2021
Progesterone receptor membrane component 1 (PGRMC1) binds and stabilizes cytochromes P450 through a heme-independent mechanism.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Genome-wide CRISPR screen reveals CGS-15943 induced heme-dependent cell death mediated by aryl hydrocarbon receptor in lung cancer cells.Apoptosis : an international journal on programmed cell death · 2026Article
- Sorghum bicolor membrane steroid binding protein 1 can bind heme and remodel ER membranes.Plant & cell physiology · 2026Article
- Progesterone receptor membrane component 1 (PGRMC1) regulates Heme trafficking through mitochondria-ER junctions.Journal of inorganic biochemistry · 2026Article
- Enhancing cross-organelle coordination to advance plant cytochrome P450 functionality in yeast.Science advances · 2025Article
- Mechanisms of heme transport in the mitochondria.Biochemical Society transactions · 2025Review
- Protein subinteractomes of human microsomal cytochromes P450.Molecular biology reports · 2025Review
- Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health.Medical review (2021) · 2024Review
- Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity.Journal of xenobiotics · 2024Review
- Article
- Quantitative analysis of the UDP-glucuronosyltransferase transcriptome in human tissues.Pharmacology research & perspectives · 2023Article
- Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis.International journal of molecular sciences · 2023Review
- Function and regulation of a steroidogenic CYP450 enzyme in the mitochondrion of Toxoplasma gondii.PLoS pathogens · 2023Article
- A proximity labeling strategy enables proteomic analysis of inter-organelle membrane contacts.iScience · 2023Article
- Hepatic progesterone receptor membrane component 1 attenuates ethanol-induced liver injury by reducing acetaldehyde production and oxidative stress.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Proteomic Analysis of Ferrochelatase Interactome in Erythroid and Non-Erythroid Cells.Life (Basel, Switzerland) · 2023Article
- PGRMC1: An enigmatic heme-binding protein.Pharmacology & therapeutics · 2023Review
- Mutant Samd9l expression impairs hematopoiesis and induces bone marrow failure in mice.The Journal of clinical investigation · 2022Article
- Biotransformation novel advances - 2021 year in review.Drug metabolism reviews · 2022Review
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Authors and funding
11 authors at 1 institution in 1 country.
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Abstract
Progesterone receptor membrane component 1 (PGRMC1) is a heme-binding protein implicated in a wide range of cellular functions. We previously showed that PGRMC1 binds to cytochromes P450 in yeast and mammalian cells and supports their activity. Recently, the paralog PGRMC2 was shown to function as a heme chaperone. The extent of PGRMC1 function in cytochrome P450 biology and whether PGRMC1 is also a heme chaperone are unknown. Here, we examined the function of Pgrmc1 in mouse liver using a knockout model and found that Pgrmc1 binds and stabilizes a broad range of cytochromes P450 in a heme-independent manner. Proteomic and transcriptomic studies demonstrated that Pgrmc1 binds more than 13 cytochromes P450 and supports maintenance of cytochrome P450 protein levels posttranscriptionally. In vitro assays confirmed that Pgrmc1 KO livers exhibit reduced cytochrome P450 activity consistent with reduced enzyme levels. Mechanistic studies in cultured cells demonstrated that PGRMC1 stabilizes cytochromes P450 and that binding and stabilization do not require PGRMC1 binding to heme. Importantly, Pgrmc1-dependent stabilization of cytochromes P450 is physiologically relevant, as Pgrmc1 deletion protected mice from acetaminophen-induced liver injury. Finally, evaluation of Y113F mutant Pgrmc1, which lacks the axial heme iron-coordinating hydroxyl group, revealed that proper iron coordination is not required for heme binding, but is required for binding to ferrochelatase, the final enzyme in heme biosynthesis. PGRMC1 was recently identified as the causative mutation in X-linked isolated pediatric cataract formation. Together, these results demonstrate a heme-independent function for PGRMC1 in cytochrome P450 stability that may underlie clinical phenotypes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.