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自噬与脂滴动态之间的联系。

Links between autophagy and lipid droplet dynamics.

机构信息

Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.

出版信息

J Exp Bot. 2022 May 13;73(9):2848-2858. doi: 10.1093/jxb/erac003.

Abstract

Autophagy is a catabolic process in which cytoplasmic components are delivered to vacuoles or lysosomes for degradation and nutrient recycling. Autophagy-mediated degradation of membrane lipids provides a source of fatty acids for the synthesis of energy-rich, storage lipid esters such as triacylglycerol (TAG). In eukaryotes, storage lipids are packaged into dynamic subcellular organelles, lipid droplets. In times of energy scarcity, lipid droplets can be degraded via autophagy in a process termed lipophagy to release fatty acids for energy production via fatty acid β-oxidation. On the other hand, emerging evidence suggests that lipid droplets are required for the efficient execution of autophagic processes. Here, we review recent advances in our understanding of metabolic interactions between autophagy and TAG storage, and discuss mechanisms of lipophagy. Free fatty acids are cytotoxic due to their detergent-like properties and their incorporation into lipid intermediates that are toxic at high levels. Thus, we also discuss how cells manage lipotoxic stresses during autophagy-mediated mobilization of fatty acids from lipid droplets and organellar membranes for energy generation.

摘要

自噬是一种分解代谢过程,其中细胞质成分被递送至液泡或溶酶体进行降解和营养物质回收。自噬介导的膜脂降解为合成能量丰富的储存脂质酯(如三酰基甘油(TAG))提供了脂肪酸的来源。在真核生物中,储存脂质被包装到动态的亚细胞细胞器——脂滴中。在能量匮乏时,脂滴可以通过自噬进行降解,这一过程称为脂噬,以释放脂肪酸通过脂肪酸β-氧化产生能量。另一方面,新出现的证据表明,脂滴对于自噬过程的有效执行是必需的。在这里,我们综述了自噬和 TAG 储存之间代谢相互作用的最新研究进展,并讨论了脂噬的机制。游离脂肪酸由于其去污剂样特性和它们在高水平时有毒的脂质中间产物的掺入而具有细胞毒性。因此,我们还讨论了细胞如何在自噬介导的从脂滴和细胞器膜中动员脂肪酸以产生能量的过程中应对脂毒性应激。

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