Anmann Tiia, Varikmaa Minna, Timohhina Natalja, Tepp Kersti, Shevchuk Igor, Chekulayev Vladimir, Saks Valdur, Kaambre Tuuli
Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia; Faculty of Science, Department of Chemistry, Tallinn University of Technology, Tallinn, Estonia.
Biochim Biophys Acta. 2014 Aug;1837(8):1350-61. doi: 10.1016/j.bbabio.2014.03.015. Epub 2014 Apr 3.
Adult cardiomyocytes have highly organized intracellular structure and energy metabolism whose formation during postnatal development is still largely unclear. Our previous results together with the data from the literature suggest that cytoskeletal proteins, particularly βII-tubulin, are involved in the formation of complexes between mitochondria and energy consumption sites. The aim of this study was to examine the arrangement of intracellular architecture parallel to the alterations in regulation of mitochondrial respiration in rat cardiomyocytes during postnatal development, from 1 day to 6 months. Respirometric measurements were performed to study the developmental alterations of mitochondrial function. Changes in the mitochondrial arrangement and cytoarchitecture of βII- and αIV-tubulin were examined by confocal microscopy. Our results show that functional maturation of oxidative phosphorylation in mitochondria is completed much earlier than efficient feedback regulation is established between mitochondria and ATPases via creatine kinase system. These changes are accompanied by significant remodeling of regular intermyofibrillar mitochondrial arrays aligned along the bundles of βII-tubulin. Additionally, we demonstrate that formation of regular arrangement of mitochondria is not sufficient per se to provide adult-like efficiency in metabolic feed-back regulation, but organized tubulin networks and reduction in mitochondrial outer membrane permeability for ADP are necessary as well. In conclusion, cardiomyocytes in rat heart become mature on the level of intracellular architecture and energy metabolism at the age of 3 months.
成年心肌细胞具有高度有序的细胞内结构和能量代谢,其在出生后发育过程中的形成仍 largely不清楚。我们之前的结果以及文献数据表明,细胞骨架蛋白,特别是βII-微管蛋白,参与了线粒体与能量消耗位点之间复合物的形成。本研究的目的是研究从出生后1天到6个月大鼠心肌细胞在发育过程中,与线粒体呼吸调节变化平行的细胞内结构排列。进行呼吸测定以研究线粒体功能的发育变化。通过共聚焦显微镜检查βII-和αIV-微管蛋白的线粒体排列和细胞结构变化。我们的结果表明,线粒体中氧化磷酸化的功能成熟比通过肌酸激酶系统在线粒体和ATP酶之间建立有效的反馈调节要早得多。这些变化伴随着沿βII-微管蛋白束排列的规则肌原纤维间线粒体阵列的显著重塑。此外,我们证明,线粒体规则排列的形成本身不足以在代谢反馈调节中提供类似成年的效率,但有组织的微管蛋白网络和降低线粒体外膜对ADP的通透性也是必要的。总之,大鼠心脏中的心肌细胞在3个月大时在细胞内结构和能量代谢水平上变得成熟。