@Article{biocell.2026.080414,
AUTHOR = {Liangliang Liu, Linjun Wang, Xin Song, Zhen Liu},
TITLE = {YOD1 Stabilizes RIPK1 via Deubiquitination to Activate NF-κB and Promote Cardiomyocyte H/R Injury},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/27110},
ISSN = {1667-5746},
ABSTRACT = {<b>Background:</b> Myocardial ischemia-reperfusion (I/R) injury represents a severe pathological process in cardiovascular diseases. This study aims to elucidate the mechanism of the yeast ovarian tumor (OTU) domain-containing protein 1 (YOD1) in cardiomyocyte injury. <b>Methods:</b> A hypoxia/reoxygenation (H/R) model was established using human AC16 cells to simulate I/R injury <i>in vitro</i>. Reverse transcription quantitative PCR (RT-qPCR) and western blotting were used to detect gene and protein expression. Cellular functions were evaluated using Cell Counting Kit-8 (CCK-8), lactate dehydrogenase (LDH), enzyme-linked immunosorbent assay (ELISA), flow cytometry, and biochemical kits. Protein interaction was validated through co-immunoprecipitation (Co-IP), ubiquitination assays, and cycloheximide (CHX) chase experiments. <b>Results:</b> YOD1 was up-regulated in H/R-induced AC16 cells (<i>p</i> &lt; 0.01). H/R decreased cell viability (<i>p</i> &lt; 0.001), superoxide dismutase (SOD) (<i>p</i> &lt; 0.001), and glutathione peroxidase 4 (GPX4) (<i>p</i> &lt; 0.001) and increased LDH (<i>p</i> &lt; 0.001), interleukin-6 (IL-6) (<i>p</i> &lt; 0.001), tumor necrosis factor-alpha (TNF-α) (<i>p</i> &lt; 0.001), reactive oxygen species (ROS) (<i>p</i> &lt; 0.001), malondialdehyde (MDA) (<i>p</i> &lt; 0.001), and Fe<sup>2+</sup> (<i>p</i> &lt; 0.001); these effects were alleviated by YOD1 knockdown (<i>p</i> &lt; 0.01). YOD1 knockdown (<i>p</i> &lt; 0.001) also reversed H/R-increased receptor-interacting serine/threonine kinase 1 (RIPK1) protein levels (<i>p</i> &lt; 0.001) and p-p65/p65 (<i>p</i> &lt; 0.001) and p-nuclear factor-kappa-B inhibitor alpha (p-IκBα)/IκBα (<i>p</i> &lt; 0.001) ratios. RIPK1 overexpression reversed the protective effects of YOD1 knockdown via activating the nuclear factor-kappa-B (NF-κB) pathway (<i>p</i> &lt; 0.01). Mechanistically, YOD1 interacted with RIPK1 and inhibited its K63-linked ubiquitination degradation (<i>p</i> &lt; 0.01). These statistical significances support the clinical potential of targeting YOD1 to mitigate inflammation, oxidative stress, and ferroptosis-related changes in myocardial I/R injury. <b>Conclusion:</b> YOD1 stabilizes RIPK1 via K63-linked ubiquitination to activate the NF-κB pathway, exacerbating inflammation, oxidative stress, and ferroptosis-related changes in H/R-induced cardiomyocytes. YOD1 may represent a potential therapeutic target for myocardial I/R injury, though further <i>in vivo</i> and clinical validation is required.},
DOI = {10.32604/biocell.2026.080414}
}