Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4D, 036 01 Martin, Slovakia.
Int J Mol Sci. 2020 Oct 18;21(20):7698. doi: 10.3390/ijms21207698.
Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics. The recent studies suggest that the interaction between Hcy and mitochondria is complex, and reactive oxygen species (ROS) are possible mediators of Hcy effects. We focus on mechanisms contributing to HHcy-associated oxidative stress, such as sources of ROS generation and alterations in antioxidant defense resulting from altered gene expression and post-translational modifications of proteins. Moreover, we discuss some recent findings suggesting that HHcy may have beneficial effects on mitochondrial ROS homeostasis and antioxidant defense. A better understanding of complex mechanisms through which Hcy affects mitochondrial functions could contribute to the development of more specific therapeutic strategies targeted at HHcy-associated disorders.
血浆同型半胱氨酸（Hcy）浓度升高，高同型半胱氨酸血症（HHcy）与各种疾病有关，包括心血管疾病和神经退行性疾病。越来越多的证据表明，这些疾病的病理生理学与线粒体功能障碍有关。在这篇综述中，我们讨论了目前关于 HHcy 对线粒体动态平衡、能量代谢、线粒体凋亡途径的影响的知识。最近的研究表明，Hcy 与线粒体之间的相互作用是复杂的，活性氧（ROS）可能是 Hcy 作用的介导物。我们专注于导致 HHcy 相关氧化应激的机制，例如 ROS 产生的来源以及抗氧化防御的改变，这是由于基因表达的改变和蛋白质的翻译后修饰。此外，我们还讨论了一些最近的发现，表明 HHcy 可能对线粒体 ROS 动态平衡和抗氧化防御有有益的影响。更好地理解 Hcy 影响线粒体功能的复杂机制，可以为针对 HHcy 相关疾病的更具体的治疗策略的发展做出贡献。
