Aung Lynn Htet Htet, Jumbo Juan Carlos Cueva, Wang Yin, Li Peifeng
Center for Molecular Genetics, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China.
Center for Bioinformatics, Institute for Translational Medicine, School of Basic Science, College of Medicine, Qingdao University, Qingdao 266021, China.
Mol Ther Nucleic Acids. 2021 Jun 24;25:416-443. doi: 10.1016/j.omtn.2021.06.006. eCollection 2021 Sep 3.
Pathological cardiac hypertrophy begins as an adaptive response to increased workload; however, sustained hemodynamic stress will lead it to maladaptation and eventually cardiac failure. Mitochondria, being the powerhouse of the cells, can regulate cardiac hypertrophy in both adaptive and maladaptive phases; they are dynamic organelles that can adjust their number, size, and shape through a process called mitochondrial dynamics. Recently, several studies indicate that promoting mitochondrial fusion along with preventing mitochondrial fission could improve cardiac function during cardiac hypertrophy and avert its progression toward heart failure. However, some studies also indicate that either hyperfusion or hypo-fission could induce apoptosis and cardiac dysfunction. In this review, we summarize the recent knowledge regarding the effects of mitochondrial dynamics on the development and progression of cardiac hypertrophy with particular emphasis on the regulatory role of mitochondrial dynamics proteins through the genetic, epigenetic, and post-translational mechanisms, followed by discussing the novel therapeutic strategies targeting mitochondrial dynamic pathways.
病理性心脏肥大最初是对工作量增加的一种适应性反应；然而，持续的血流动力学应激会导致其发生适应不良，最终发展为心力衰竭。线粒体作为细胞的动力源，在心脏肥大的适应性和适应不良阶段均能对其进行调节；它们是动态细胞器，可通过一个称为线粒体动力学的过程来调整自身的数量、大小和形状。最近，多项研究表明，促进线粒体融合并同时防止线粒体分裂，可在心脏肥大期间改善心脏功能，并避免其向心力衰竭发展。然而，一些研究也表明，过度融合或分裂不足都可能诱导细胞凋亡和心脏功能障碍。在本综述中，我们总结了有关线粒体动力学对心脏肥大发生发展影响的最新知识，特别强调了线粒体动力学蛋白通过遗传、表观遗传和翻译后机制所发挥的调节作用，随后讨论了针对线粒体动态途径的新型治疗策略。
