He Haojia, Han Zhuoxue, Cheng Shuai, Zhou You
School of Basic Medical Sciences, Hebei University, Baoding 071002, China.
School of Basic Medical Sciences, Hebei University, Baoding 071002, China; Key Laboratory of Aging and Health in Hebei Province, Baoding 071002, China.
Neurobiol Dis. 2025 Sep;213:107030. doi: 10.1016/j.nbd.2025.107030. Epub 2025 Jul 11.
Sensorineural hearing loss (SNHL) is a prevalent and complex auditory disorder with a multifactorial pathogenesis, in which mitochondrial dysfunction plays a pivotal role. Mitochondria are abundantly localized in critical structures of the inner ear, where they not only provide the substantial energy required for auditory transduction but also regulate key cellular processes. Growing evidence suggests that mitochondrial impairment, characterized by excessive reactive oxygen species (ROS) generation, dysregulated inflammatory responses, disrupted apoptosis, and mitochondrial DNA (mtDNA) mutations, is closely linked to the onset and progression of SNHL. Recent advances in mitochondria-targeted therapeutic strategies, such as antioxidant delivery, promotion of mitochondrial biogenesis, and mitochondrial gene therapy, have shown promising preclinical results. However, significant challenges remain in translating these approaches into clinical practice, particularly in terms of targeted delivery, long-term efficacy, and potential side effects. This comprehensive review systematically examines the molecular mechanisms underlying mitochondrial involvement in SNHL pathogenesis, evaluates recent progress in mitochondria-targeted interventions, and discusses current limitations and future directions in this rapidly evolving field. By integrating current knowledge and identifying key research gaps, this review aims to provide a solid theoretical foundation and fresh perspectives for the development of effective therapeutic strategies for SNHL.
感音神经性听力损失（SNHL）是一种常见且复杂的听觉障碍，其发病机制具有多因素性，其中线粒体功能障碍起着关键作用。线粒体大量存在于内耳的关键结构中，它们不仅为听觉转导提供所需的大量能量，还调节关键的细胞过程。越来越多的证据表明，以活性氧（ROS）过度产生、炎症反应失调、细胞凋亡紊乱和线粒体DNA（mtDNA）突变为特征的线粒体损伤与SNHL的发生和发展密切相关。线粒体靶向治疗策略的最新进展，如抗氧化剂递送、促进线粒体生物发生和线粒体基因治疗，已显示出有前景的临床前结果。然而，将这些方法转化为临床实践仍面临重大挑战，特别是在靶向递送、长期疗效和潜在副作用方面。这篇综述系统地研究了线粒体参与SNHL发病机制的分子机制，评估了线粒体靶向干预的最新进展，并讨论了这一快速发展领域的当前局限性和未来方向。通过整合现有知识并确定关键研究差距，本综述旨在为开发有效的SNHL治疗策略提供坚实的理论基础和新的视角。
