Kang Sun Woo Sophie, Fu Dong
Aging and Alzheimers Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, The University of Sydney and Concord Hospital, Concord, Australia; Faculty of Pharmacy, The University of Sydney, Australia.
Faculty of Pharmacy, The University of Sydney, Australia; Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Crit Rev Eukaryot Gene Expr. 2019;29(5):483-497. doi: 10.1615/CritRevEukaryotGeneExpr.2019029911.
Hepatocytes have well-defined polarized morphological structure. Establishment and maintenance of cellular polarity is crucial to the function and viability of hepatocytes. Many disorders, both genetic and acquired, and drugs can impair hepatocyte polarization resulting in liver dysfunction and injury. Hepatocyte polarization is an energy-dependent cellular process. Hence, cellular energy metabolism can significantly affect the polarized morphology and function of hepatocytes. Recent in vitro studies have demonstrated that multiple cellular organelles, including mitochondria, auto-phagosomes and lipid droplets, are involved in the utilization of energy for hepatocyte polarization; also, AMP-dependent kinase (AMPK), a key cellular energy sensor, regulates the function and activities of these cellular organelles and thus plays an important role in bioenergetics for hepatocyte polarization. This review provides the latest understanding on how mitochondria, autophagosomes, and lipid droplets coordinate energy production, and it addresses how AMPK activation regulates these key cellular organelles for energy production during hepatocyte polarization. Furthermore, the review suggests potential directions for future research.
肝细胞具有明确的极化形态结构。细胞极性的建立和维持对于肝细胞的功能和生存能力至关重要。许多遗传性和后天性疾病以及药物都会损害肝细胞极化,导致肝功能障碍和损伤。肝细胞极化是一个能量依赖的细胞过程。因此,细胞能量代谢可显著影响肝细胞的极化形态和功能。最近的体外研究表明,包括线粒体、自噬体和脂滴在内的多种细胞器参与了肝细胞极化的能量利用;此外,AMP依赖激酶(AMPK)作为关键的细胞能量传感器,调节这些细胞器的功能和活性,从而在肝细胞极化的生物能量学中发挥重要作用。本综述提供了关于线粒体、自噬体和脂滴如何协调能量产生的最新认识,并阐述了AMPK激活如何在肝细胞极化过程中调节这些关键细胞器以进行能量产生。此外,该综述还提出了未来研究的潜在方向。