García-Ruiz Carmen, Kaplowitz Neil, Fernandez-Checa José C
Department of Cell Death and Proliferation, Institute of Biomedical Research of Barcelona (IIBB), Consejo Superior Investigaciones Cientificas (CSIC) and Liver Unit-Hospital Clinic and CIBEREHD, Barcelona, Spain.
Southern California Research Center for ALPD and Cirrhosis, Keck School of Medicine of the University of Southern, California, Los Angeles, CA, USA.
Curr Pathobiol Rep. 2013 Sep 1;1(3):159-168. doi: 10.1007/s40139-013-0021-z.
Alcohol-induced liver disease (ALD) is a major health concern of alcohol abuse and a leading cause of liver-related morbidity and mortality. The pathogenesis of ALD is multifactorial and still ill characterized. One of the hallmarks of ALD common for both patients and experimental models is the alteration in the architecture and function of mitochondria. Due to their primordial role in energy production, metabolism and cell fate decisions, these changes in mitochondria caused by alcohol are considered an important contributory factor in ALD. A better understanding of the mechanisms underlying alcohol-mediated mitochondrial alterations may shed light on ALD pathogenesis and provide novel avenues for treatment. The purpose of the current review is to briefly update the latest developments in ALD research regarding morphological and functional mitochondrial regulation including mitochondrial dynamics and biogenesis, mitochondrial protein acetylation and evidence for an endoplasmic reticulum stress-mitochondrial cholesterol link of potential relevance for ALD.
酒精性肝病(ALD)是酒精滥用引起的主要健康问题,也是肝脏相关发病和死亡的主要原因。ALD的发病机制是多因素的,目前仍不清楚。ALD患者和实验模型共有的一个标志是线粒体结构和功能的改变。由于线粒体在能量产生、代谢和细胞命运决定中起主要作用,酒精引起的这些线粒体变化被认为是ALD的一个重要促成因素。更好地理解酒精介导的线粒体改变的潜在机制,可能有助于揭示ALD的发病机制,并提供新的治疗途径。本综述的目的是简要介绍ALD研究中关于线粒体形态和功能调节的最新进展,包括线粒体动力学和生物发生、线粒体蛋白乙酰化,以及内质网应激与线粒体胆固醇联系的证据,这些证据可能与ALD相关。