Jaishy Bharat, Abel E Dale
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
J Lipid Res. 2016 Sep;57(9):1619-35. doi: 10.1194/jlr.R067520. Epub 2016 Jun 21.
Lipids are essential components of a cell providing energy substrates for cellular processes, signaling intermediates, and building blocks for biological membranes. Lipids are constantly recycled and redistributed within a cell. Lysosomes play an important role in this recycling process that involves the recruitment of lipids to lysosomes via autophagy or endocytosis for their degradation by lysosomal hydrolases. The catabolites produced are redistributed to various cellular compartments to support basic cellular function. Several studies demonstrated a bidirectional relationship between lipids and lysosomes that regulate autophagy. While lysosomal degradation pathways regulate cellular lipid metabolism, lipids also regulate lysosome function and autophagy. In this review, we focus on this bidirectional relationship in the context of dietary lipids and provide an overview of recent evidence of how lipid-overload lipotoxicity, as observed in obesity and metabolic syndrome, impairs lysosomal function and autophagy that may eventually lead to cellular dysfunction or cell death.
脂质是细胞的重要组成部分,为细胞过程提供能量底物、信号中间体以及生物膜的构建模块。脂质在细胞内不断循环和重新分布。溶酶体在这一循环过程中发挥重要作用,该过程涉及通过自噬或内吞作用将脂质招募到溶酶体,以便由溶酶体水解酶进行降解。产生的分解代谢产物被重新分配到细胞的各个区室,以支持基本的细胞功能。多项研究表明脂质与溶酶体之间存在调节自噬的双向关系。虽然溶酶体降解途径调节细胞脂质代谢,但脂质也调节溶酶体功能和自噬。在本综述中,我们聚焦于饮食脂质背景下的这种双向关系,并概述近期有关脂质过载脂毒性(如在肥胖症和代谢综合征中观察到的)如何损害溶酶体功能和自噬(最终可能导致细胞功能障碍或细胞死亡)的证据。