ArticleCell death discovery2021
Autophagy is induced and modulated by cholesterol depletion through transcription of autophagy-related genes and attenuation of flux.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- FDFT1 Acts as a Negative Regulator of Autophagy by Modulating AMPK-ULK1 Signaling in Hepatocellular Carcinoma Cells.Biomolecules & therapeutics · 2026Article
- Cholesterol Deficiency Directs Autophagy-Dependent Secretion of Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- NSC777201 exhibits anticancer activity against colorectal cancer cells by inducing multiple types of cell death.Cancer cell international · 2025Article
- HMG-CoA reductase inhibition preserves testicular function after torsion/detorsion by modulating oxidative stress and AKT signaling.Scientific reports · 2025Article
- Lysine p-nitroanilide impairs cellular energetics and potentiates statin-induced cytotoxicity in RD rhabdomyosarcoma cells.PloS one · 2025Article
- Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults.Nutrients · 2024Article
- ER-associated VAP27-1 and VAP27-3 proteins functionally link the lipid-binding ORP2A at the ER-chloroplast contact sites.Nature communications · 2024Article
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Protective Effects of Lovastatin in a Population-Based ALS Study and Mouse Model.Annals of neurology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Perturbations to cellular homeostasis, including reduction of the cholesterol level, induce autophagy, a self-digestion process of cellular constituents through an autophagosomal-lysosomal pathway. In accord with its function as a membrane organizer and metabolic sentinel, the cellular response to cholesterol depletion comprises multiple phenomena, including the activation of transcriptional responses, accumulation of reactive oxygen species (ROS), and activation of stress-related signaling pathways. However, the molecular mechanisms by which cholesterol depletion regulates autophagy and the putative involvement of transcriptional responses, ROS and/or stress-related signaling in autophagy regulation in this biological context are not fully understood. Here, we find that cholesterol depletion regulates autophagy at three different levels. First, employing RNA-seq, we show that cholesterol depletion increases the expression of autophagy-related genes independent of ROS or JNK activity. Second, analysis of LC3 lipidation and intracellular localization, and of p62 levels and degradation kinetics, reveals that cholesterol depletion mediates autophagy induction while interfering with autophagic flux. Of note, only the latter depends on ROS accumulation and JNK activity. In view of the common use of cholesterol-reducing drugs as therapeutic agents, our findings have important implications for multiple cellular settings in which autophagy plays a prominent role.
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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.