2. Academic Validation
  3. Sestrin 2 deficiency exacerbates noise-induced cochlear injury through inhibiting ULK1/Parkin-mediated mitophagy

Sestrin 2 deficiency exacerbates noise-induced cochlear injury through inhibiting ULK1/Parkin-mediated mitophagy

  • Antioxid Redox Signal. 2022 Jun 16. doi: 10.1089/ars.2021.0283.
Yalan Li 1 2,  Shengsheng Li 3,  Liyuan Wu 4 5,  Tingting Wu 4 6,  Mengxiao Li 4 7,  Deliang Du 4 8,  Yalin Chen 4 9,  Caiji Wang 4 10,  Xuanyi Li 11,  Shili Zhang 4 12,  Zeqi Zhao 13,  Liting Zheng 4 14,  Mengbing Chen 4 15,  Menghua Li 4 16,  Ting Li 17,  Xi Shi 4 18,  Yuehua Qiao 4 19 20
Affiliations

Affiliations

  • 1 Xuzhou Medical University, 38044, Institute of Audiology and Balance Science, Xuzhou, China.
  • 2 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; shengya_li@126.com.
  • 3 Jiangsu University, 12676, Department of Neurosurgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China; ylss20161215@163.com.
  • 4 Xuzhou Medical University, 38044, Institute of Audiology and Balance Science, Xuzhou, Jiangsu, China.
  • 5 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; wuliyuan95@163.com.
  • 6 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; real_wtt@163.com.
  • 7 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; limengxiao0229@outlook.com.
  • 8 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; dudl0415@163.com.
  • 9 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; chenyl1228@163.com.
  • 10 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; caiji1983@126.com.
  • 11 Xuzhou Medical University, 38044, Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; otologistli@163.com.
  • 12 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; 18361202569@163.com.
  • 13 Xuzhou Medical University, 38044, Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; zeqi_zhao@163.com.
  • 14 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; zheng_liting@sina.cn.
  • 15 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; cmb9209@163.com.
  • 16 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; lmh0920@126.com.
  • 17 Xuzhou Medical University, 38044, School of Life Sciences Xuzhou Medical University, Xuzhou, Jiangsu, China; tingli8@xzhmu.edu.cn.
  • 18 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China; shixi19850112@126.com.
  • 19 Xuzhou Medical University, 38044, The Artificial Auditory Laboratory of Jiangsu Province, Xuzhou, Jiangsu, China.
  • 20 Xuzhou Medical University, 38044, Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; yhqiao@xzhmu.edu.cn.
PMID: 35708118 DOI: 10.1089/ars.2021.0283
Abstract

Aims: Noise damage to auditory hair cells is associated with oxidative stress and mitochondrial dysfunction. This study was aimed to investigate the possible effect of sestrin 2 (SESN2), an endogenous antioxidant protein, on noise-induced hearing loss (NIHL) and the underlying mechanisms.

Results: We identified SESN2 as a protective factor against oxidative stress in NIHL via activation of Parkin-mediated Mitophagy. Consistently, SESN2 expression was increased and Mitophagy was induced during the early stage after a temporary threshold shift (TTS) due to noise exposure or H2O2 stimulation; conversely, SESN2 deficiency blocked Mitophagy and exacerbated acoustic trauma. Mechanistically, SESN2 interacted with Unc-51-like protein kinase 1 (ULK1), promoting ULK1 pro-tein level stabilization by interfering with its proteasomal degradation. This stabili-zation is essential for Mitophagy initiation, since restoring ULK1 expression in SESN2-silenced cells rescued Mitophagy defects. Innovation & Conclusion: Our results provide novel insights regarding SESN2 as a therapeutic target against noise-induced cochlear injury, possibly through improved Mitophagy.

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