journal article·2026-03Open access

XIAP Stabilizes DDRGK1 to Promote ER‐Phagy and Protects Against Noise‐Induced Hearing Loss

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

Advanced Science· Volume 13· Issue 18

Abstract

ABSTRACT Noise‐induced hearing loss (NIHL) is a common cause of acquired sensorineural hearing loss. Excessive endoplasmic reticulum (ER) stress‐induced apoptosis of cochlear hair cells contributes to NIHL. ER autophagy (ER‐phagy) is a critical pathway for maintaining ER homeostasis and cell survival. DDRGK1 (DDRGK domain containing 1) is a crucial receptor in ER‐phagy, essential for the removal of injured ER components. This work investigates the involvement of DDRGK1‐mediated ER‐phagy in NIHL, which has remained unclear. ER‐phagy flux is inhibited in HEI‐OC1 cells treated with hydrogen peroxide. Noise exposure reduces XIAP (X‐linked inhibitor of apoptosis protein) and DDRGK1 protein levels in these cells. Moreover, XIAP binds to DDRGK1, increasing the stability of DDRGK1 and activating ER‐phagy. Notably, in noise‐exposed CBA/CaJ mice, gastrodin, a traditional Chinese medicine ingredient, reduces noise‐induced loss of cochlear hair cells, ribbon synaptic damage, and hearing loss by promoting XIAP expression, thereby increasing DDRGK1 protein levels and activating ER‐phagy. These findings highlight XIAP‐DDRGK1‐mediated ER‐phagy as a novel therapeutic target for NIHL treatment.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Autophagy in Disease and Therapy · Endoplasmic Reticulum Stress and Disease · Cell death mechanisms and regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Otolaryngology‐Head and Neck Surgery The Second Affiliated Hospital of Anhui Medical University Hefei China

School of Life Sciences Anhui Medical University Hefei China

State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute For Life and Health Jiangsu Province High‐Tech Key Laboratory for Bio‐Medical Research Southeast University Nanjing China

Co‐Innovation Center of Neuroregeneration Nantong University Nantong China

Department of Neurology School of Life Science Beijing Institute of Technology Aerospace Center Hospital Beijing China

Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China

Southeast University Shenzhen Research Institute Shenzhen China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · China Postdoctoral Science Foundation · Natural Science Foundation of Jiangsu Province · Science and Technology Department of Sichuan Province · Shenzhen Science and Technology Innovation Program

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