Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress.
Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress.
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DOI：
10.1155/2013/327167
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发表时间：
2013
影响因子：
--
通讯作者：
Kim HP
中科院分区：
文献类型：
--
作者：
Lee SJ;Zhang J;Choi AM;Kim HP
脂滴(LD)的形成是细胞应激的标志。细胞试图通过将其代谢从氧化磷酸化转换为糖酵解来对抗有害刺激，从而节省LDS中用于产生细胞还原能力和合成代谢生物合成的资源。膜磷脂也是LDS的来源之一。为了阐明LDS的形成，我们将小鼠暴露在由盲肠结扎和穿孔(CLP)引起的高氧、低氧、心肌缺血和脓毒症中。所有上述应激源都促进了LDS的形成，通过电子显微镜观察，线粒体严重肿胀。耗尽线粒体DNA的线粒体(ρ0细胞)的破坏显著增加了LDS的形成，导致脂肪酸生物合成的转录激活和代谢重新编程为糖酵解。血红素氧合酶(HO)-1中和CLP介导的败血症休克小鼠模型。在HO-1基因缺陷的小鼠中，在CLP上没有观察到LD的形成，但观察到“LD修饰蛋白”的伴随减少，这意味着LDS与细胞保护活性之间存在联系。总之，应激过程中LD的生物发生可以触发适应性LD的形成，这取决于线粒体的完整性和HO-1的活性；这可能是一种细胞生存策略，将能量生成底物分配给细胞防御。
Lipid droplet (LD) formation is a hallmark of cellular stress. Cells attempt to combat noxious stimuli by switching their metabolism from oxidative phosphorylation to glycolysis, sparing resources in LDs for generating cellular reducing power and for anabolic biosynthesis. Membrane phospholipids are also a source of LDs. To elucidate the formation of LDs, we exposed mice to hyperoxia, hypoxia, myocardial ischemia, and sepsis induced by cecal ligation and puncture (CLP). All the above-mentioned stressors enhanced the formation of LDs, as assessed by transmission electron microscopy, with severe mitochondrial swelling. Disruption of mitochondria by depleting mitochondrial DNA (ρ0 cells) significantly augmented the formation of LDs, causing transcriptional activation of fatty acid biosynthesis and metabolic reprogramming to glycolysis. Heme oxygenase (HO)-1 counteracts CLP-mediated septic shock in mouse models. In HO-1-deficient mice, LD formation was not observed upon CLP, but a concomitant decrease in “LD-decorating proteins” was observed, implying a link between LDs and cytoprotective activity. Collectively, LD biogenesis during stress can trigger adaptive LD formation, which is dependent on mitochondrial integrity and HO-1 activity; this may be a cellular survival strategy, apportioning energy-generating substrates to cellular defense.
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DOI：
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