ArticleBone research2024
IRF1-mediated upregulation of PARP12 promotes cartilage degradation by inhibiting PINK1/Parkin dependent mitophagy through ISG15 attenuating ubiquitylation and SUMOylation of MFN1/2.
Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
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- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Semaglutide targets the Isg15-FUNDC1 axis: suppressing IFN-β overactivation and attenuating blood-brain barrier injury in diabetic intracerebral hemorrhage.Journal of neuroinflammation · 2026Article
- Functionalized hydrogels of CeOMaterials today. Bio · 2026Article
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Integrative bioinformatics-machine learning-experimental validation identifies shared immunomodulatory targets in psoriasis and psoriatic arthritis and deciphers allicin's therapeutic mechanism.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- Traditional Chinese medicine-derived monomers protect chondrocytes and delay osteoarthritis progression by regulating mitochondrial quality control.Frontiers in molecular biosciences · 2026Review
- Multimodal modulation of metal-based nanomaterials in osteoarthritis immunotherapy: current landscape and future paradigms.Frontiers in immunology · 2026Review
- A novel role of the TNF-α/p65/IRF1 axis in aggravating rheumatoid arthritis through the induction of fibroblast-like synoviocytes pyroptosis.Frontiers in pharmacology · 2026Article
- Organelle-centered ISG15 biology: distinguishing covalent ISGylation from interferon-associated responses.Frontiers in immunology · 2026Review
- Mitochondrial transplantation for osteoarthritis: from molecular mechanisms to clinical translation.Frontiers in immunology · 2026Review
- Identification and validation of SUMOylation-related key genes for osteoarthritis through integration of single-cell, bulk RNA sequencing and animal model experiments.Frontiers in medicine · 2026Article
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial quality control mechanisms as molecular targets for impaired lung development: from fetuses to neonates.Respiratory research · 2025Review
- Mitochondrial fission and fusion in inflammatory diseases: mechanisms and therapeutic implications.Journal of translational medicine · 2025Review
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Review
- Post-translational modifications orchestrate mTOR-driven cell death in cardiovascular disease.Frontiers in cardiovascular medicine · 2025Review
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11 authors.
Funding
Abstract
Osteoarthritis (OA) is an age-related cartilage-degenerating joint disease. Mitochondrial dysfunction has been reported to promote the development of OA. Poly (ADP-ribose) polymerase family member 12 (PARP12) is a key regulator of mitochondrial function, protein translation, and inflammation. However, the role of PARP12 in OA-based cartilage degradation and the underlying mechanisms are relatively unknown. Here, we first demonstrated that PARP12 inhibits mitophagy and promotes OA progression in human OA cartilage and a monosodium iodoacetate-induced rat OA model. Using mass spectrometry and co-immunoprecipitation assay, PARP12 was shown to interact with ISG15, upregulate mitofusin 1 and 2 (MFN1/2) ISGylation, which downregulated MFN1/2 ubiquitination and SUMOylation, thereby inhibiting PINK1/Parkin-dependent chondrocyte mitophagy and promoting cartilage degradation. Moreover, inflammatory cytokine-induced interferon regulatory factor 1 (IRF1) activation was required for the upregulation of PARP12 expression, and it directly bound to the PARP12 promoter to activate transcription. XAV-939 inhibited PARP12 expression and suppressed OA pathogenesis in vitro and in vivo. Clinically, PARP12 can be used to predict the severity of OA; thus, it represents a new target for the study of mitophagy and OA progression. In brief, the IRF1-mediated upregulation of PARP12 promoted cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy via ISG15-based attenuation of MFN1/2 ubiquitylation and SUMOylation. Our data provide new insights into the molecular mechanisms underlying PARP12-based regulation of mitophagy and can facilitate the development of therapeutic strategies for the treatment of OA.
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