Wang Zhao V, Hill Joseph A
Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA.
Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA.
Cell Metab. 2015 Feb 3;21(2):215-226. doi: 10.1016/j.cmet.2015.01.016.
The prevalence of heart disease, especially heart failure, continues to increase, and cardiovascular disease remains the leading cause of death worldwide. As cardiomyocytes are essentially irreplaceable, protein quality control is pivotal to cellular homeostasis and, ultimately, cardiac performance. Three evolutionarily conserved mechanisms-autophagy, the unfolded protein response, and the ubiquitin-proteasome system-act in concert to degrade misfolded proteins and eliminate defective organelles. Recent advances have revealed that these mechanisms are intimately associated with cellular metabolism. Going forward, comprehensive understanding of the role of protein quality control mechanisms in cardiac pathology will require integration of metabolic pathways and metabolic control.
心脏病,尤其是心力衰竭的患病率持续上升,心血管疾病仍是全球主要死因。由于心肌细胞基本不可替代,蛋白质质量控制对于细胞内稳态乃至心脏功能至关重要。三种进化上保守的机制——自噬、未折叠蛋白反应和泛素-蛋白酶体系统——协同作用以降解错误折叠的蛋白质并清除有缺陷的细胞器。最近的进展表明,这些机制与细胞代谢密切相关。展望未来,要全面了解蛋白质质量控制机制在心脏病理学中的作用,需要整合代谢途径和代谢调控。