线粒体功能障碍相关遗传性非综合征型听力损失的研究进展

Progress in Research on Hereditary Non-syndromic Hearing Loss Associated with Mitochondrial Dysfunctions

线粒体拥有独立于核基因存在的遗传物质,其功能障碍可引起多种疾病,包括遗传性非综合征性听力损失。其致病机制可能与听觉系统细胞对能量需求及氧化磷酸化依赖性较高,线粒体基因突变影响重要蛋白质功能,导致氧化磷酸化过程异常,ROS-AMPK-E2F1通路激活,最终引起内耳细胞损伤和凋亡有关。本文综述了近年来与遗传性非综合征型听力损失相关的人类线粒体基因突变研究进展以及典型的研究动物模型,从组织细胞和分子层面阐述线粒体功能障碍引发的听力损失及其发生机制,并总结其对于临床治疗和缓解相关听力损失的指导意义。

Mitochondria possess genetic materials independent of the nuclear genes.Mitochondrial dysfunctions cause a variety of diseases including hereditary non-syndromic hearing loss.Auditory cells that operate on high energy expenditure from oxidative phosphorylation require high level of mitochondrial activities.Mitochondrial gene mutations that affect the functions of important proteins result in abnormal oxidative phosphorylation processes,which in turn trigger downstream activation of ROS-AMPK-E2F1 pathway and cause damage and apoptosis of inner ear cells.This paper reviews a few recently established animal models used in studies of human mitochondrial gene mutations associated with hereditary non-syndromic hearing loss.The review summarizes underlying cellular and molecular mechanisms in several types of hearing loss due to mitochondrial dysfunctions.Clinical relevance and future treatment regimens are also discussed.