Li Xinhang, Zhu Yalin, Ruiz-Lozano Pilar, Wei Ke
Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, P.R. China.
National Heart and Lung Institute, Imperial College London, London, UK.
Cell Regen. 2024 Jan 31;13(1):2. doi: 10.1186/s13619-024-00186-x.
The regenerative capacity of the adult mammalian heart remains a formidable challenge in biological research. Despite extensive investigations into the loss of regenerative potential during evolution and development, unlocking the mechanisms governing cardiomyocyte proliferation remains elusive. Two recent groundbreaking studies have provided fresh perspectives on mitochondrial-to-nuclear communication, shedding light on novel factors that regulate cardiomyocyte proliferation. The studies identified two mitochondrial processes, fatty acid oxidation and protein translation, as key players in restricting cardiomyocyte proliferation. Inhibition of these processes led to increased cell cycle activity in cardiomyocytes, mediated by reduction in H3k4me3 levels through accumulated α-ketoglutarate (αKG), and activation of the mitochondrial unfolded protein response (UPR), respectively. In this research highlight, we discuss the novel insights into mitochondrial-to-nuclear communication presented in these studies, the broad implications in cardiomyocyte biology and cardiovascular diseases, as well as the intriguing scientific questions inspired by the studies that may facilitate future investigations into the detailed molecular mechanisms of cardiomyocyte metabolism, proliferation, and mitochondrial-to-nuclear communications.
成年哺乳动物心脏的再生能力仍是生物学研究中一项艰巨的挑战。尽管对进化和发育过程中再生潜力丧失进行了广泛研究，但揭示调控心肌细胞增殖的机制仍不清楚。最近两项开创性研究为线粒体与细胞核之间的通讯提供了新视角，揭示了调节心肌细胞增殖的新因子。这些研究确定了脂肪酸氧化和蛋白质翻译这两个线粒体过程是限制心肌细胞增殖的关键因素。抑制这些过程分别通过累积的α-酮戊二酸（αKG）降低H3k4me3水平以及激活线粒体未折叠蛋白反应（UPR），导致心肌细胞的细胞周期活性增加。在本研究亮点中，我们讨论了这些研究中关于线粒体与细胞核通讯的新见解、对心肌细胞生物学和心血管疾病的广泛影响，以及这些研究引发的有趣科学问题，这些问题可能有助于未来对心肌细胞代谢、增殖和线粒体与细胞核通讯详细分子机制的研究。
