ArticleNature communications2023
A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Low temperature rather than hypoxia drives cholesterol synthesis and oxygen consumption in plateau zokors.iScience · 2026Article
- Lactate-mediated cholesterol uptake promotes liver cancer progression via the SCARB1-autophagy axis.EMBO reports · 2026Article
- PER2 reprograms intracellular cholesterol synthesis to inhibit oral squamous cell carcinoma and the chronotherapeutic efficacy of simvastatin.Cell death discovery · 2026Article
- LRP1 in atherosclerosis: a hierarchical view of regulatory mechanisms and epigenetic knowledge gaps.Frontiers in cell and developmental biology · 2026Review
- Oxygenation: Nanotechnological Strategies for Conquering Tumor Hypoxia in Photodynamic Therapy.International journal of nanomedicine · 2026Review
- Global characterization of Dictyostelium discoideum gene and protein expression changes under hypoxic conditions.BMC genomics · 2025Article
- March6 Protects Against Acute Kidney Injury by Suppressing Renal Tubular Epithelial Cell Ferroptosis Through the Destabilization of P53 and ACSL4 Proteins.Inflammation · 2025Article
- A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation.Nature communications · 2025Article
- TiORegenerative biomaterials · 2025Article
- SREBP2 as a central player in cancer progression: potential for targeted therapeutics.Frontiers in pharmacology · 2025Review
- Hypoxia exposure impairs male fertility via inhibiting Septin2-mediated spermatogonial proliferation.Human reproduction open · 2025Article
- Hypoxic Memory Mediates Prolonged Tumor-Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression.Cancer research · 2024Article
- Metabolic ripple effects - deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment.Disease models & mechanisms · 2024Review
- Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.Frontiers in cell and developmental biology · 2024Review
- Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity.BMJ oncology · 2024Review
- A tale of 2 gasses, 1 regulator, and cholesterol homeostasis.PLoS biology · 2023Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), the key transcription factor driving sterol production in mammals, as an oxygen-sensitive regulator of cholesterol synthesis. SREBP2 degradation in hypoxia overrides the normal sterol-sensing response, and is HIF independent. We identify MARCHF6, through its NADPH-mediated activation in hypoxia, as the main ubiquitin ligase controlling SREBP2 stability. Hypoxia-mediated degradation of SREBP2 protects cells from statin-induced cell death by forcing cells to rely on exogenous cholesterol uptake, explaining why many solid organ tumours become auxotrophic for cholesterol. Our findings therefore uncover an oxygen-sensitive pathway for governing cholesterol synthesis through regulated SREBP2-dependent protein degradation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.