ArticleAging cell2022
Chaperone-mediated autophagy degrades Keap1 and promotes Nrf2-mediated antioxidative response.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 82 citations in OpenAlex.
- Dietary Modulation of CMA: Implications for Cancer Prevention and Therapy.Physiology (Bethesda, Md.) · 2027Review
- Bone marrow stromal cells promote chemoresistance in acute myeloid leukaemia through P2RX7-mediated antioxidant defence.Experimental & molecular medicine · 2026Article
- Hypoxia and Oxidation Pathway Crosstalk in Head and Neck Squamous Cell Carcinoma.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- Dimethyl fumarate ameliorates quinolinic acid-induced ageing and neurodegeneration in Caenorhabditis elegans.Biogerontology · 2026Article
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Defective chaperone-mediated autophagy in the retinal pigment epithelium of age-related macular degeneration patients.EMBO molecular medicine · 2025Article
- 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
- Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration.Bone research · 2025Article
- A Novel Hybrid Peptide VLP-Aβ Exhibits Antioxidant Activity In Vitro and In Vivo via KEAP1-NRF2-ARE Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Management of ROS and Regulatory Cell Death in Myocardial Ischemia-Reperfusion Injury.Molecular biotechnology · 2025Review
- Baicalin plays a protective role by regulating ferroptosis in multiple diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.Autophagy · 2025Article
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Mechanisms of Copper-Induced Autophagy and Links with Human Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Hybridization Design and High-Throughput Screening of Peptides with Immunomodulatory and Antioxidant Activities.International journal of molecular sciences · 2025Article
- Blue Light Damages Retinal Ganglion Cells Via Endoplasmic Reticulum Stress and Autophagy in Chickens.Investigative ophthalmology & visual science · 2025Article
- Microvascular endothelial dysfunction in vascular senescence and disease.Frontiers in cardiovascular medicine · 2025Review
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of oxidative stress is highly intertwined with aging process and contributes to aging-related diseases, such as neurodegenerative diseases. Deciphering the molecular machinery that regulates oxidative stress is fundamental to further uncovering the pathogenesis of these diseases. Chaperone-mediated autophagy (CMA), a highly selective lysosome-dependent degradation process, has been proven to be an important maintainer of cellular homeostasis through multiple mechanisms, one of which is the attenuation of oxidative stress. However, the specific mechanisms underlying this antioxidative action of CMA are not fully understood. In this study, we found that CMA directly degrades Kelch-like ECH-associated protein 1 (Keap1), an adaptor of E3 ligase complex that promotes the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a master transcriptional regulator in antioxidative response. Activated CMA induced by prolonged oxidative stress led to an increase in Nrf2 level by effectively degrading Keap1, contributing to Nrf2 nuclear translocation and the expression of multiple downstream antioxidative genes. Meanwhile, together with previous study showing that Nrf2 can also transcriptionally regulate LAMP2A, the rate-limiting factor of CMA process, we reveal a feed-forward loop between CMA and Nrf2. Our study identifies CMA as a previously unrecognized regulator of Keap1-Nrf2 pathway and reinforces the antioxidative role of CMA.
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