ArticleExperimental & molecular medicine2023
SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Sirtuins in intervertebral disc degeneration: current understanding.Molecular medicine (Cambridge, Mass.) · 2024Pooled it
- Endothelial PARP1 orchestrates endothelial-to-mesenchymal transition via the PARylation of FHL2 in ischaemic heart failure.Acta pharmacologica Sinica · 2026Article
- Identification of key molecules and pathways in CaOx crystal-induced renal injury based on metabolomics and proteomics.International urology and nephrology · 2026Article
- SIRT5 mediates the pro-osteogenic effects of estrogen through FDX1 demalonylation and cuproptosis inhibition in mesenchymal stem cells.Genes & diseases · 2026Article
- The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.Nature communications · 2026Article
- Disruption of YAP biomolecular condensates by mechanical stress drives intervertebral disc vascularization.Science advances · 2026Article
- MoCox6 is a regulator of mitophagy and a druggable target in Magnaporthe oryzae.Nature microbiology · 2026Article
- TDP43 cytoplasmic mislocalization initiates mitochondrial dysfunction and intercellular senescence propagation in intervertebral disc degeneration.Experimental & molecular medicine · 2026Article
- Elevated TRIM25 Impairs Poly (ADP-ribose) Metabolism via PARG Degradation and Mediates Compression-Induced Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Methylene blue restores NADJournal of orthopaedic translation · 2026Article
- Functionalized hydrogels of CeOMaterials today. Bio · 2026Article
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Ciliary IFT88 inhibits intervertebral disc degeneration under excessive mechanical stress by regulating endplate cartilage calcification.Journal of advanced research · 2026Article
- Mitochondrial dysfunction in the pathogenesis of intervertebral disc herniation: a mitochondrial related genome-wide Mendelian randomization analysis.Journal of translational medicine · 2026Article
- The UBC/SIRT5/DRP1 axis regulates mitochondrial dynamics to alleviate Staphylococcus aureus-induced oxidative stress and senescence in bovine mammary epithelial cells.PLoS pathogens · 2026Article
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating FOXP1 SUMOylation.International journal of biological sciences · 2026Article
- [Salvianolic acid B promotes mitochondrial homeostasis and improves cardiac function in mice with ischemia-reperfusion injury by inhibiting Sirt1 protein degradation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Sirtuin Family in Acute Kidney Injury: Insights into Cellular Mechanisms and Potential Targets for Treatment.Biomolecules · 2025Review
- Melatonin attenuates intervertebral disc degeneration by restoring mitochondrial homeostasis through PGC-1α signaling pathway.Cellular and molecular life sciences : CMLS · 2025Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction plays a major role in the development of intervertebral disc degeneration (IDD). Sirtuin 5 (SIRT5) participates in the maintenance of mitochondrial homeostasis through its desuccinylase activity. However, it is still unclear whether succinylation or SIRT5 is involved in the impairment of mitochondria and development of IDD induced by excessive mechanical stress. Our 4D label-free quantitative proteomic results showed decreased expression of the desuccinylase SIRT5 in rat nucleus pulposus (NP) tissues under mechanical loading. Overexpression of Sirt5 effectively alleviated, whereas knockdown of Sirt5 aggravated, the apoptosis and dysfunction of NP cells under mechanical stress, consistent with the more severe IDD phenotype of Sirt5 KO mice than wild-type mice that underwent lumbar spine instability (LSI) surgery. Moreover, immunoprecipitation-coupled mass spectrometry (IP-MS) results suggested that AIFM1 was a downstream target of SIRT5, which was verified by a Co-IP assay. We further demonstrated that reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress. Finally, we validated the efficacy of treatments targeting disrupted mitochondrial protein importation by upregulating SIRT5 expression or methylene blue (MB) administration in the compression-induced rat IDD model. In conclusion, our study provides new insights into the occurrence and development of IDD and offers promising therapeutic approaches for IDD.
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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.