ArticleAutophagy2020
Dysregulation of TFEB contributes to manganese-induced autophagic failure and mitochondrial dysfunction in astrocytes.
Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 124 citations in OpenAlex.
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Molecular psychiatry · 2026Article
- The Role of Mitochondrial Quality Control in Manganese-induced Neurotoxicity.Neurotoxicity research · 2025Review
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Research square · 2025Article
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Dihydromyricetin restores lysosomal function in Schwann cells to alleviate bortezomib-induced peripheral neuropathy via ERK/TFEB signaling.Archives of toxicology · 2025Article
- c-Abl/TFEB Pathway Activation as a Common Pathogenic Mechanism in Lysosomal Storage Diseases: Therapeutic Potential of c-Abl Inhibitors.Antioxidants (Basel, Switzerland) · 2025Article
- Role of manganese in brain health and disease: Focus on oxidative stress.Free radical biology & medicine · 2025Review
- Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Exposure to Manganese Induces Autophagy-Lysosomal Pathway Dysfunction-Mediated Tauopathy by Activating the cGAS-STING Pathway in the Brain.Environment & health (Washington, D.C.) · 2025Article
- Manganese exposure induces parkinsonism-like symptoms by Serpina3n-TFEB-v/p-ATPase signaling mediated lysosomal dysfunction.Cell biology and toxicology · 2025Article
- From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies.International journal of molecular sciences · 2024Review
- Dihydromyricetin suppresses endothelial NLRP3 inflammasome activation and attenuates atherogenesis by promoting mitophagy.Lipids in health and disease · 2024Article
- Signal Transduction Associated with Mn-induced Neurological Dysfunction.Biological trace element research · 2024Review
- From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death.Apoptosis : an international journal on programmed cell death · 2024Review
- MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.Journal of cellular and molecular medicine · 2024Article
- Effects of Manganese and Iron, Alone or in Combination, on Apoptosis in BV2 Cells.Biological trace element research · 2024Article
- Crosstalk between autophagy and ferroptosis mediate injury in ischemic stroke by generating reactive oxygen species.Heliyon · 2024Review
- Research Progress on the Mechanism of Lysosome in Myocardial Ischemia-Reperfusion Injury Based on Autophagy.Reviews in cardiovascular medicine · 2024Review
- Heavy Metal Mediated Progressive Degeneration and Its Noxious Effects on Brain Microenvironment.Biological trace element research · 2024Review
- A partial Drp1 knockout improves autophagy flux independent of mitochondrial function.Molecular neurodegeneration · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Epidemiological and clinical studies have long shown that exposure to high levels of heavy metals are associated with increased risks of neurodegenerative diseases. It is widely accepted that autophagic dysfunction is involved in pathogenesis of various neurodegenerative disorders; however, the role of heavy metals in regulation of macroautophagy/autophagy is unclear. Here, we show that manganese (Mn) induces a decline in nuclear localization of TFEB (transcription factor EB), a master regulator of the autophagy-lysosome pathway, leading to autophagic dysfunction in astrocytes of mouse striatum. We further show that Mn exposure suppresses autophagic-lysosomal degradation of mitochondria and induces accumulation of unhealthy mitochondria. Activation of autophagy by rapamycin or TFEB overexpression ameliorates Mn-induced mitochondrial respiratory dysfunction and reactive oxygen species (ROS) generation in astrocytes, suggesting a causal relation between autophagic failure and mitochondrial dysfunction in Mn toxicity. Taken together, our data demonstrate that Mn inhibits TFEB activity, leading to impaired autophagy that is causally related to mitochondrial dysfunction in astrocytes. These findings reveal a previously unappreciated role for Mn in dysregulation of autophagy and identify TFEB as a potential therapeutic target to mitigate Mn toxicity. ABBREVIATIONS: BECN1: beclin 1; CTSD: cathepsin D; DMEM: Dulbecco's Modified Eagle Medium; GFAP: glial fibrillary acid protein; GFP: green fluorescent protein; HBSS: hanks balanced salt solution; LAMP: lysosomal-associated membrane protein; LDH: lactate dehydrogenase; Lys Inh: lysosomal inhibitors; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; Mn: manganese; MTOR: mechanistic target of rapamycin kinase; OCR: oxygen consumption rate; PBS: phosphate-buffered saline; PFA: paraformaldehyde; PI: propidium iodide; ROS: reactive oxygen species; s.c.: subcutaneous; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB.
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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.