Abstract
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.
Highlights
Intracellular lipid droplets (LDs) store neutral lipids, including triacylglycerol and cholesterol esters, in cells [1]
LDs are surrounded by a unique phospholipid monolayer that is decorated with many proteins, among which adipocyte differentiation-related protein (ADRP) and the perilipin family are well characterized [2,3,4]
Alveolar type II cells were more sensitive to high oxygen inhalation in terms of LD biogenesis (Figures 1(b) and 1(c))
Summary
Intracellular lipid droplets (LDs) store neutral lipids, including triacylglycerol and cholesterol esters, in cells [1]. The biology of LDs has gained public interest because of the causal link between excess lipid storage in certain tissues and pathophysiologies related to obesity [9, 10]. In these cases, LDs are likely to interfere with membrane trafficking of the insulin-sensitive glucose transporter, which might account for the insulin resistance common in patients with type 2 diabetes [11]. Many kinds of cellular stress, including inflammation and oxidative stress, can induce LD biogenesis [15, 16] In these cases, it is hypothesized that fatty acids may serve a protective role against the stressors
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