ArticleAutophagy2014
Disruption of chaperone-mediated autophagy-dependent degradation of MEF2A by oxidative stress-induced lysosome destabilization.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- Dual mechanism of human ATG10S in suppressing MEF2A-Driven pro-inflammatory responses.Autophagy · 2026Article
- Acetylation Regulates ACSL4 Degradation Through Chaperone-Mediated Autophagy to Alleviate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chaperone-Mediated Autophagy Reactivation Protects Against Severe Acute Pancreatitis-Associated Liver Injury Through Upregulating Keap1/Nrf2 Signaling Pathway and Inhibiting NLRP3 Inflammasome Activation.Cell biochemistry and biophysics · 2025Article
- Identification and verification of oxidative stress-related genes in the diagnosis of osteoporosis.Scientific reports · 2025Article
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- Article
- ALKBH1 promotes HIF-1α-mediated glycolysis by inhibiting N-glycosylation of LAMP2A.Cellular and molecular life sciences : CMLS · 2024Article
- Chaperone-mediated autophagy: Molecular mechanisms, biological functions, and diseases.MedComm · 2023Review
- Myocyte Enhancer Factor 2A Plays a Central Role in the Regulatory Networks of Cellular Physiopathology.Aging and disease · 2023Review
- The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration.International journal of molecular sciences · 2023Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Article
- Review
- Cell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma.International journal of molecular sciences · 2022Review
- The Role of Macroautophagy and Chaperone-Mediated Autophagy in the Pathogenesis and Management of Hepatocellular Carcinoma.Cancers · 2022Review
- Chaperone-mediated autophagy and disease: Implications for cancer and neurodegeneration.Molecular aspects of medicine · 2021Article
- MEF2A transcriptionally upregulates the expression of ZEB2 and CTNNB1 in colorectal cancer to promote tumor progression.Oncogene · 2021Article
- Decreased MEF2A Expression Regulated by Its Enhancer Methylation Inhibits Autophagy and May Play an Important Role in the Progression of Alzheimer's Disease.Frontiers in neuroscience · 2021Article
- Inhibition of tumor suppressor p73 by nerve growth factor receptor via chaperone-mediated autophagy.Journal of molecular cell biology · 2020Article
- Mitophagy in the Pathogenesis of Liver Diseases.Cells · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress has been implicated in both normal aging and various neurodegenerative disorders and it may be a major cause of neuronal death. Chaperone-mediated autophagy (CMA) targets selective cytoplasmic proteins for degradation by lysosomes and protects neurons against various extracellular stimuli including oxidative stress. MEF2A (myocyte enhancer factor 2A), a key transcription factor, protects primary neurons from oxidative stress-induced cell damage. However, the precise mechanisms of how the protein stability and the transcriptional activity of MEF2A are regulated under oxidative stress remain unknown. In this study, we report that MEF2A is physiologically degraded through the CMA pathway. In pathological conditions, mild oxidative stress (200 μM H 2O 2) enhances the degradation of MEF2A as well as its activity, whereas excessive oxidative stress (> 400 μM H 2O 2) disrupts its degradation process and leads to the accumulation of nonfunctional MEF2A. Under excessive oxidative stress, an N-terminal HDAC4 (histone deacetylase 4) cleavage product (HDAC4-NT), is significantly induced by lysosomal serine proteases released from ruptured lysosomes in a PRKACA (protein kinase, cAMP-dependent, catalytic, α)-independent manner. The production of HDAC4-NT, as a MEF2 repressor, may account for the reduced DNA-binding and transcriptional activity of MEF2A. Our work provides reliable evidence for the first time that MEF2A is targeted to lysosomes for CMA degradation; oxidative stress-induced lysosome destabilization leads to the disruption of MEF2A degradation as well as the dysregulation of its function. These findings may shed light on the underlying mechanisms of pathogenic processes of neuronal damage in various neurodegenerative-related diseases.
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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.