ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
FBXO2 Alleviates Intervertebral Disc Degeneration via Dual Mechanisms: Activating PINK1-Parkin Mitophagy and Ubiquitinating LCN2 to Suppress Ferroptosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- A "Progenitor Cell Ark" hydrogel system for intervertebral disc regeneration via mitochondrial targeting and mitophagy enhancement.Science advances · 2026Article
- Dual-Gene Edited Extracellular Vesicles Remodel the Redox Homeostasis to Inhibit Ferroptosis in Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nuciferine-Loaded Lipid Nanoparticle Microneedles Alleviate Intervertebral Disc Degeneration by Restoring Nucleus Pulposus Cell Homeostasis.Pharmaceutics · 2026Article
- Biomaterial-based strategies targeting ferroptosis for alleviating intervertebral disc degeneration: Advances and perspectives.Journal of orthopaedic translation · 2026Review
- Targeting the Fra2/LCN2 axis attenuates PMRedox biology · 2026Article
- Ubiquitination in intervertebral disc degeneration: from mechanisms to potential therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Protective effect of pentoxifylline against high-glucose-induced ferroptosis in vascular smooth muscle cells.Journal of molecular endocrinology · 2026Article
- Mitochondria-driven ferroptosis in intervertebral disc degeneration: A novel target in age-related spinal diseases (Review).Experimental and therapeutic medicine · 2026Review
- PHB2 mitigates intervertebral disc degeneration by modulating mitophagy to inhibit necroptosis in nucleus pulposus cells.iScience · 2026Article
- Lipocalin 2: a double-edged sword in cellular ferroptosis.Cell biology and toxicology · 2026Review
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- FBXO11 and FBXO32 are associated with TRAF3-TBK1-IRF3 signaling components in chronic hepatitis B: evidence from clinical samples and preliminary mechanistic studies.American journal of translational research · 2026Article
- Parkin protects against traumatic brain injury through regulating mitochondrial quality control.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Iron, lipid peroxidation and discogenic pain: a redox framework for ferroptosis in intervertebral disc degeneration.Frontiers in cell and developmental biology · 2026Review
- PINK1 overexpression suppresses p38 MAPK/NF‑κB signaling to attenuate chondrocyte senescence in osteoarthritis.International journal of molecular medicine · 2025Article
- miR-188-5p accelerates intervertebral disc degeneration by mediating P4HB to regulate ferroptosis in nucleus pulposus cells.European journal of medical research · 2025Article
- Integrated mendelian randomization and bioinformatics approach unveiling the immunological and prognostic significance of FBXO2 in breast cancer.Discover oncology · 2025Article
- FBXO2 Alleviates Intervertebral Disc Degeneration via Dual Mechanisms: Activating PINK1-Parkin Mitophagy and Ubiquitinating LCN2 to Suppress Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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8 authors.
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Abstract
Intervertebral disc degeneration (IVDD), a leading cause of chronic low back pain, arises from nucleus pulposus (NP) cell dysfunction due to oxidative stress-induced mitophagy impairment and ferroptosis, though regulatory mechanisms remain unclear. F-box only protein 2 (FBXO2), a Kruppel-like factor 10 (KLF10)-regulated F-box protein, is downregulated in degenerated human NP tissues and correlates with disease severity. Overexpression of FBXO2 restores extracellular matrix (ECM) homeostasis by promoting matrix component synthesis and inhibiting catabolic enzymes, while its knockdown exacerbates ECM degradation. Under oxidative stress, FBXO2 activates PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy, restoring mitochondrial membrane potential and reducing reactive oxygen species (ROS) accumulation. Proteomics reveals that FBXO2 suppresses ferroptosis by attenuating lipid peroxidation, glutathione depletion, and iron overload. Mechanistically, FBXO2 binds lipocalin-2 (LCN2) via its FBA domain, promoting K27-linked polyubiquitination to drive proteasomal degradation of this ferroptosis inducer. FBXO2 co-expression reverses LCN2-induced mitochondrial dysfunction and ferroptosis markers. In vivo, adeno-associated virus 9 (AAV9)-mediated overexpression of FBXO2 ameliorates IVDD in rats, whereas FBXO2 knockout (KO) mice exhibit exacerbated IVDD. LCN2 silencing in FBXO2-deficient mice partially restores disc integrity and matrix component expression. These findings identify FBXO2 as a dual regulator coordinating mitophagy activation and ferroptosis suppression, offering therapeutic potential for IVDD progression.
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