线粒体逆行信号——治疗相关疾病的新途径

Mitochondrial retrograde signaling: a new option for the treatment of mitochondrially related diseases

线粒体在细胞代谢过程中发挥关键作用,除了合成ATP外,还参与许多生理病理过程,包括细胞凋亡、炎症、氧化应激、神经元病变、肿瘤发生发展和衰老等。大多数线粒体蛋白质的基因转录发生在细胞核中,因此线粒体的生物发生和线粒体稳态的维持主要取决于核基因(nuclear DNA, nDNA)的表达以及线粒体-细胞核相互作用。反之,线粒体可以通过核转录因子而影响核内基因的表达,称为线粒体逆行信号(mitochondrial retrograde signaling)。本文综合线粒体-细胞核逆行信号的传导过程及调控机制的研究进展,阐述线粒体调控核内基因的途径和影响生命活动的机制,探讨线粒体逆行信号与疾病的关系及疾病治疗新策略。

Mitochondria play a key role in cell metabolism. In addition to synthesizing ATP, they also participate in many physiological and pathological processes, including apoptosis, inflammation, oxidative stress, neuronal disease, tumor development, and aging. Most gene transcription of mitochondrial proteins occurs in the nucleus, so the biogenesis of mitochondria and the maintenance of mitochondrial homeostasis mainly depend on the expression of nuclear genes(nDNA) and mitochondria-nucleus interactions. Conversely, mitochondria can affect the expression of nuclear genes through nuclear transcription factors, a process called mitochondrial retrograde signaling. This review summarizes the research progress on mitochondria-nucleus retrograde signaling and its regulation, including the ways by which mitochondria regulate nuclear genes and affect biological processes, and discusses new strategies for the treatment of diseases that involve mitochondrial retrograde signaling in disease pathology.