天津体育学院天津市运动生理学与运动医学重点实验室,天津 301617
Q5;Q7
国家自然科学基金(31971100) 资助项目。
Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin 301617, China
This work was supported by a grant from The National Natural Science Foundation of China (31971100).
心衰长久以来一直缺少有效治疗方法,给社会造成了巨大的经济和民生负担,新诊断标志物的确认和治疗方法的研发十分迫切。线粒体功能障碍与心衰发生和发展密切相关,以线粒体为基础的能量供应紊乱、钙失衡、氧化应激和细胞死亡在心衰的发展中起着重要作用,但线粒体调控的具体机制还不十分清楚。非编码RNA被证实在表观调控、转录后修饰、翻译调节等多方面发挥重要调控作用。研究表明,包括miRNA、lncRNA、circRNA在内的大量非编码RNA在心脏发育和心脏疾病发展过程中存在差异表达,并在线粒体蛋白稳态、氧化磷酸化、氧化应激、凋亡与自噬等调控中发挥了重要作用,进而影响心衰等心脏疾病的发生发展,但其详细机制尚未完全阐明。本文就近年心衰发生和发展过程中非编码RNA调控线粒体功能机制的相关研究进行综述,梳理了近年来非编码RNA在调节线粒体结构与功能进而影响心衰发展方面的研究进展,以期为心衰研究与治疗提供新的思路和靶点。
Heart failure is a complex cardiac disease without effect therapeutic methods, which causes a huge economic and social burden. It is urgent to identify new diagnostic biomarker and develop new therapeutic method. Mitochondria dysfunction is closely associated with the development of heart failure. About 95% ATP consumed by heart are derived from mitochondrial oxidative phosphorylation. The deficiency of myocardial energy supply caused by mitochondrial injury is the key factor linking the mitochondrial dysfunction to heart failure, which involves mitochondrial mediated metabolism disorder, calcium imbalance, oxidative stress, apoptosis and mitophagy. It has been demonstrated that non-coding RNA (ncRNA) playing a critical role in modulating epigenetic modification, post-transcription, translation modification and so on. Many researches showed that ncRNA express abnormally during the heart development and cardiac disease, and exhibit important regulating roles in the regulation of mitochondrial structure and function. Among them, miRNA has been demonstrated widely. Most miRNA, originated from either nuclear or mitochondrial genome, showed important roles in regulating heart pathophysiology change through mitochondrial dysfunction and structure disruption via targeting mRNA or protein. While lncRNA and circRNA play diverse roles in the regulation of mitochondrial structure and function by ncRNA-miRNA-mRNA triple networks, which provide us more perspective to understand the explicit role of ncRNA in mitochondria and heart pathophysiology. However, only a little ncRNA encoded by mitochondrial genome have been confirmed in the process of heart failure. Besides, it is still unclear that how does the ncRNA encoded by nuclear genome transport to mitochondria and vice versa. Moreover, recent studies discovered many other mitochondria encoded ncRNA, such as piRNA and small ncRNA shorter than 200 nucleotides derived from tRNA, rRNA or lncRNA, play important roles in many diseases. It has a broad prospect in investigating the various roles of mitochondria encoded ncRNA. Therefore, this work aims to provide some new ideas and targets for the clinical research and therapy for heart failure via reviewing the newly recent researches about the regulation mechanism of new ncRNAs on mitochondria function in the process of heart failure.
王硕,赵云罡.心衰进程中非编码RNA对线粒体功能的调控作用[J].生物化学与生物物理进展,2023,50(7):1538-1552
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