Brown David I, Parry Traci L, Willis Monte S
McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Compr Physiol. 2017 Jun 18;7(3):841-862. doi: 10.1002/cphy.c160024.
Heart failure (HF) is a costly and deadly syndrome characterized by the reduced capacity of the heart to adequately provide systemic blood flow. Mounting evidence implicates pathological changes in cardiac energy metabolism as a contributing factor in the development of HF. While the main source of fuel in the healthy heart is the oxidation of fatty acids, in the failing heart the less energy efficient glucose and glycogen metabolism are upregulated. The ubiquitin proteasome system plays a key role in regulating metabolism via protein-degradation/regulation of autophagy and regulating metabolism-related transcription and cell signaling processes. In this review, we discuss recent research that describes the role of the ubiquitin-proteasome system (UPS) in regulating metabolism in the context of HF. We focus on ubiquitin ligases (E3s), the component of the UPS that confers substrate specificity, and detail the current understanding of how these E3s contribute to cardiac pathology and metabolism. © 2017 American Physiological Society. Compr Physiol 7:841-862, 2017.
心力衰竭（HF）是一种代价高昂且致命的综合征，其特征是心脏充分提供全身血流的能力下降。越来越多的证据表明，心脏能量代谢的病理变化是HF发生发展的一个促成因素。在健康心脏中，主要的能量来源是脂肪酸氧化，而在衰竭心脏中，能量利用效率较低的葡萄糖和糖原代谢则上调。泛素蛋白酶体系统在通过蛋白质降解/自噬调节以及调节代谢相关转录和细胞信号转导过程来调控代谢方面发挥着关键作用。在本综述中，我们讨论了最近的研究，这些研究描述了泛素 - 蛋白酶体系统（UPS）在HF背景下调节代谢中的作用。我们重点关注泛素连接酶（E3s），它是UPS中赋予底物特异性的成分，并详细阐述了目前对这些E3s如何导致心脏病理和代谢的理解。© 2017美国生理学会。综合生理学7:841 - 862，2017。
