XIAP Stabilizes DDRGK1 to Promote ER-Phagy and Protect Against Noise-Induced Hearing Loss

    January 2026 in “ Advanced Science ”
    Lin Yan, Yuhua Zhang, Jiawei Du, Yongjun Zhu, Wei Cao, Yongjie Wei, Han Wu, Shiyu Qiu, Shiyi Pan, Lian Chen, Pingping Liang, Renjie Chai, Jianming Yang, Qiaojun Fang
    The study explores the role of DDRGK1-mediated ER-phagy in noise-induced hearing loss (NIHL), revealing that ER-phagy is crucial for maintaining ER homeostasis and cell survival. It was found that noise exposure decreases XIAP and DDRGK1 protein levels, inhibiting ER-phagy. XIAP binds to DDRGK1, enhancing its stability and activating ER-phagy. In noise-exposed CBA/CaJ mice, gastrodin, a traditional Chinese medicine ingredient, mitigates cochlear hair cell loss, synaptic damage, and hearing loss by promoting XIAP expression, which increases DDRGK1 levels and activates ER-phagy. These results suggest that targeting XIAP-DDRGK1-mediated ER-phagy could be a novel therapeutic approach for treating NIHL.
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