Mizushima Wataru, Takahashi Hidehisa, Watanabe Masashi, Kinugawa Shintaro, Matsushima Shouji, Takada Shingo, Yokota Takashi, Furihata Takaaki, Matsumoto Junichi, Tsuda Masaya, Chiba Ikuru, Nagashima Shun, Yanagi Shigeru, Matsumoto Masaki, Nakayama Keiichi I, Tsutsui Hiroyuki, Hatakeyama Shigetsugu
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan; Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
J Mol Cell Cardiol. 2016 Nov;100:43-53. doi: 10.1016/j.yjmcc.2016.09.013. Epub 2016 Sep 25.
A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction. Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure. Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207-interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure.
衰竭的心脏表现出严重的能量不足，据推测这种能量短缺在心脏功能障碍的发展中起关键作用。然而，关于导致衰竭心脏能量代谢改变的机制却知之甚少。在此，我们表明在心脏中特异性表达的新型泛素连接酶207（RNF207）在心脏能量代谢中发挥作用。新生大鼠心肌细胞（NRCs）中RNF207的缺失导致细胞内三磷酸腺苷（ATP）浓度降低和线粒体功能障碍。与这一结果一致，我们在此观察到在患有包括心力衰竭在内的常见心脏疾病的小鼠中，RNF207的表达显著降低。有趣的是，蛋白质组学方法揭示RNF207与电压依赖性阴离子通道（VDAC）相互作用，VDAC被认为是线粒体功能的关键调节因子，是一种与RNF207相互作用的蛋白质。我们的研究结果表明RNF207参与心肌细胞的ATP生成，提示RNF207在心力衰竭的发展中起重要作用。
