ArticleThe Journal of cell biology2005
Lithium induces autophagy by inhibiting inositol monophosphatase.
Article in The Journal of cell biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 503 papers, 2 of them syntheses that pooled it.
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.
A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1 Antitrypsin Deficiency
Evaluation of Lithium Efficacy Against Chemotherapy Induced Neutropenia in Breast Cancer Patients
Who cites it
503 citing papers in PubMed, 2 syntheses or guidelines pooled it, 966 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- Effect of lithium on chemotherapy-induced neutropenia in Egyptian breast cancer patients; a prospective clinical study.Cancer chemotherapy and pharmacology · 2024Trial
- A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder.Journal of child and adolescent psychopharmacology · 2021Trial
- The role of sphingolipids in major depressive disorder and associated cognitive impairment: interactions with monoaminergic signaling, neuroinflammation, and neurogenesis.Molecular psychiatry · 2026Review
- The lithium-magnesium-zinc axis under stress: regulation of N-glycosylation-linked proteostasis and Alzheimer's disease.Inflammopharmacology · 2026Review
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Myo-inositol metabolism in two high-performance laying hen strains at different production periods.Poultry science · 2026Article
- Glucosamine Promotes Autophagy and Attenuates Hepatic Steatosis Via O-GlcNAcylation-Mediated Mechanisms.Journal of biochemical and molecular toxicology · 2026Article
- IP3R2-mediated inter-organelle calcium signaling suppresses melanosome degradation.PLoS biology · 2026Article
- Lithium as a Potential Neuroprotective Strategy in Glaucoma: Mechanisms and Therapeutic Perspectives.Biomolecules · 2026Review
- Lithium Chloride-Induced Nuclear Envelope Remodeling in 3D Endometrial Cancer Spheroids.International journal of molecular sciences · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Lysosome-Acidifying Nanoparticles Rescue A30P α-Synuclein Induced Neuronal Death in Cellular and Drosophila Models of Parkinson's Disease.Advanced healthcare materials · 2026Article
- Lithium's effects on serum neurofilament light in Parkinson's disease: A post hoc analysis.IBRO neuroscience reports · 2026Article
- Article
- Liver Structure after Administration of Autophagy-Modifying Drugs in Mice with Experimental Skin Melanoma.Bulletin of experimental biology and medicine · 2026Article
- Cytostatic and Non-Apoptotic Effects of Vinorelbine-Based Therapy in 3D Endometrial Cancer Spheroids.Biology · 2026Article
- No evidence lithium supplementation extends lifespan in male Drosophila melanogaster.Biogerontology · 2026Article
- Lithium and the Brain-Bone Axis: A Bridge between Osteoporosis and Alzheimer's Disease.Current osteoporosis reports · 2026Review
443 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Macroautophagy is a key pathway for the clearance of aggregate-prone cytosolic proteins. Currently, the only suitable pharmacologic strategy for up-regulating autophagy in mammalian cells is to use rapamycin, which inhibits the mammalian target of rapamycin (mTOR), a negative regulator of autophagy. Here we describe a novel mTOR-independent pathway that regulates autophagy. We show that lithium induces autophagy, and thereby, enhances the clearance of autophagy substrates, like mutant huntingtin and alpha-synucleins. This effect is not mediated by glycogen synthase kinase 3beta inhibition. The autophagy-enhancing properties of lithium were mediated by inhibition of inositol monophosphatase and led to free inositol depletion. This, in turn, decreased myo-inositol-1,4,5-triphosphate (IP3) levels. Our data suggest that the autophagy effect is mediated at the level of (or downstream of) lowered IP3, because it was abrogated by pharmacologic treatments that increased IP3. This novel pharmacologic strategy for autophagy induction is independent of mTOR, and may help treatment of neurodegenerative diseases, like Huntington's disease, where the toxic protein is an autophagy substrate.
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.