ArticleCirculation research2024
Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.
Article in Circulation research, 2024. 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.
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- Cell-Type-Specific Calibration of Mitochondrial Ubiquitination in Stem Cell Fate Decisions.Stem cell reviews and reports · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction.Biomedicines · 2026Article
- Enhancing Mitophagy with PEP-1-CAT Attenuates Vascular Inflammation and Atherogenesis in Mice.Inflammation · 2026Article
- Review
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- STUB1-mediated PGC-1α ubiquitination promotes postoperative cognitive dysfunction in aged mice via modulating autophagy-lysosome machinery.European journal of medical research · 2025Article
- RNA Modifications in Health and Disease.MedComm · 2025Review
- RING-Box E3 Ligase Target N-Terminal Lysine 55 to Regulate Turnover of Sp7 Protein.Journal of cellular biochemistry · 2025Article
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
- The multifaceted role of autophagy and mitophagy in cardiovascular health and disease.Autophagy reports · 2025Review
- Article
- Disulfidptosis-Related Genes as Novel Biomarkers and Therapeutic Targets in Dilated Cardiomyopathy.Journal of inflammation research · 2025Article
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy.International journal of biological sciences · 2024Article
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15 authors.
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Abstract
backgroundClearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. Apart from Parkin, little is known about additional Ub (ubiquitin) ligases that mediate mitochondrial ubiquitination and turnover, particularly in highly metabolically active organs such as the heart.
methodsIn this study, we have combined in silico analysis and biochemical assay to identify CRL (cullin-RING ligase) 5 as a mitochondrial Ub ligase. We generated cardiomyocytes and mice lacking RBX2 (RING-box protein 2; also known as SAG [sensitive to apoptosis gene]), a catalytic subunit of CRL5, to understand the effects of RBX2 depletion on mitochondrial ubiquitination, mitophagy, and cardiac function. We also performed proteomics analysis and RNA-sequencing analysis to define the impact of loss of RBX2 on the proteome and transcriptome.
resultsRBX2 and CUL (cullin) 5, 2 core components of CRL5, localize to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, increased cardiomyocyte cell death, and has a global impact on the mitochondrial proteome. In vivo, deletion of the
conclusionsThese findings identify RBX2-CRL5 as a mitochondrial Ub ligase that regulates mitophagy and cardiac homeostasis in a Parkin-independent, PINK1-dependent manner.
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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 Socratic graph.