ArticleAutophagy2025
Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.
Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells.Nature aging · 2026Article
- Chaperone-mediated autophagy in physiological homeostasis, disease and ageing.Nature reviews. Molecular cell biology · 2026Review
- Mechanical stress-mediated ferritinophagy aggravates cartilage endplate degeneration via a PIEZO1-NCOA4-ZBP1 axis.Autophagy · 2026Article
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Article
- Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.The journal of gene medicine · 2026Article
- Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteostasis Dysfunction and Heat Shock Protein Networks in Intervertebral Disc Degeneration: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal Degradation.Angewandte Chemie (International ed. in English) · 2026Article
- Itgb1-Mediated Stabilization of Vimentin Alleviates Excessive Mechanical Stress-Induced Nucleus Pulposus Cell Pyroptosis and Intervertebral Disc Degeneration via PINK1-Parkin-Dependent Mitophagy.Cell proliferation · 2026Article
- Mechanism of Netrin-1 in electroacupuncture-mediated inhibition of nerve fiber ingrowth in degenerative intervertebral discs.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Microenvironment-educated MSC-EVs loaded injectable smart hydrogel for targeting senescent nucleus pulposus cells and inhibiting ferroptosis against intervertebral disc degeneration.Bioactive materials · 2026Article
- The role and potential therapeutic intervention of cellular senescence in intervertebral disc degeneration.Genes & diseases · 2026Review
- Advances in the study of macrophage polarization in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- A continuous DNA repairing system for alleviating intervertebral disc degeneration.Journal of nanobiotechnology · 2026Article
- Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer's disease.Genes & diseases · 2026Review
- Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanism of action and clinical application of autophagy in multiple sclerosis (Review).International journal of molecular medicine · 2026Review
- Integrated Molecular Docking and Network-Based Analysis Reveals Multitarget Interaction Patterns of Nutraceutical Compounds in Intervertebral Disc Degeneration.Biomedicines · 2026Article
- Epigenetic H3K4me3 activation of miR-155-5p promotes intervertebral disc degeneration via autophagy and ageing in nucleus pulposus cells.Non-coding RNA research · 2026Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in chaperone-mediated autophagy (CMA) are associated with cellular senescence, but the mechanism remains poorly understood. Here, we found that CMA inhibition induced cellular senescence in a calcium-dependent manner and identified its role in TNF-induced senescence of nucleus pulposus cells (NPC) and intervertebral disc degeneration. Based on structural and functional proteomic screens, PLCG1 (phospholipase C gamma 1) was predicted as a potential substrate for CMA deficiency to affect calcium homeostasis. We further confirmed that PLCG1 was a key mediator of CMA in the regulation of intracellular calcium flux. Aberrant accumulation of PLCG1 caused by CMA blockage resulted in calcium overload, thereby inducing NPC senescence. Immunoassays on human specimens showed that reduced LAMP2A, the rate-limiting protein of CMA, or increased PLCG1 was associated with disc senescence, and the TNF-induced disc degeneration in rats was inhibited by overexpression of
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