Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.
Int J Mol Sci. 2021 Feb 18;22(4):2007. doi: 10.3390/ijms22042007.
The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a "vicious circle" in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.
线粒体呼吸链是细胞中活性氧(ROS)产生的主要部位。尽管线粒体具有强大的抗氧化系统,但过量的 ROS 不能被完全中和,累积的氧化损伤可能导致线粒体在能量产生方面的效率降低,以及 ROS 过量的增加,这被认为会导致抗氧化/氧化机制的严重失衡和线粒体损伤的“恶性循环”。由于能量产生不足,慢性暴露于过量 ROS 会导致包括核酸、蛋白质、脂质和氨基酸在内的生命重要生物分子的氧化损伤。不同形式的线粒体功能障碍(线粒体病)可能影响大脑、心脏、周围神经和内分泌系统、眼睛、耳朵、肠道和肾脏等器官。因此,线粒体病已被提出作为一个有吸引力的诊断靶点,用于研究任何原因不明的进行性多系统疾病的患者。本文综述了线粒体病的发病机制,详细介绍了先进的分析工具,并提出了预测方法、靶向预防和医疗服务的个性化,作为管理与线粒体病相关的级联病理的整体手段。