USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.
W, F., XX, T., J, Z., YX, H., H, L., Z, W., TW, W., L, L., & GJ, Z. (2026). USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.. JCI insight. https://doi.org/10.1172/jci.insight.195761
W F, XX T, J Z, YX H, H L, Z W, et al. USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.. JCI insight. 2026; doi: 10.1172/jci.insight.195761
W F, XX T, J Z, et al. USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.[J]. JCI insight. 2026. DOI: 10.1172/jci.insight.195761.
@article{w2026,
author = {Fu W and Tian XX and Zhou J and Huang YX and Li H and Wang Z and Wei TW and Li L and Zhao GJ},
title = {USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.},
journal = {JCI insight},
year = {2026},
doi = {10.1172/jci.insight.195761},
note = {PMID: 42635049},
}
TY - JOUR AU - Fu W AU - Tian XX AU - Zhou J AU - Huang YX AU - Li H AU - Wang Z AU - Wei TW AU - Li L AU - Zhao GJ TI - USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1. T2 - JCI insight PY - 2026 DO - 10.1172/jci.insight.195761 AN - PMID:42635049 ER -
Atrial fibrillation (AF) contributes to cardiovascular morbidity and mortality. Ubiquitin-specific peptidase 10 (USP10) plays a crucial role in numerous cellular processes; however, its particular role in AF remains largely unexplored. In the present study, USP10 expression was assessed in human atrial samples and angiotensin II-treated (Ang II-treated) mouse atrial tissues. An Ang II-induced AF mouse model was employed to investigate the effects of USP10 on atrial remodeling and AF susceptibility. Calcium imaging and patch clamp techniques were used to evaluate USP10's influence on calcium handling and triggered activity. Additionally, RNA sequencing, coimmunoprecipitation, and ubiquitination assays were performed to explore the regulatory interactions between USP10 and NADH:ubiquinone oxidoreductase subunit S1 (NDUFS1). Our findings demonstrate that USP10 is downregulated in atrial tissues from mouse models and patients with AF. USP10 overexpression counteracts Ang II-induced atrial remodeling and reduces AF susceptibility. Furthermore, USP10 contributes to the restoration of mitochondrial function in AF. Mechanistically, USP10 deubiquitinates NDUFS1 at lysine 621, stabilizing NDUFS1 protein levels and mitigating Ang II-induced mitochondrial dysfunction. This study uncovers a critical mechanistic link between USP10 and NDUFS1. Our findings suggest that upregulating USP10 or targeting NDUFS1 degradation could provide an alternative therapeutic strategy to mitigate AF progression and associated cardiovascular risk.