Mitochondrial Dysfunction Induces Formation of Lipid Droplets as a Generalized Response to Stress

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.

Changes in ultrastructural features of the foraminifera Ammonia spp. in response to anoxic conditions: Field and laboratory observations

“…Other environmental stressors, such as heavy metal toxicity, have been linked to increases in the lipid contents of both marine dinoflagellates (Prévot and Soyer, 1978) and benthic foraminifera (Le Cadre and Debenay, 2006;Frontalini et al, 2016;Frontalini et al, 2017). In mammals, lipid droplet formation has been shown to be a cellular response to detrimental environmental conditions, with cells switching from oxidative phosphorylation to glycolysis and fatty acid synthesis in response to mitochondrial dysfunction, and sequestering resources in lipid droplets (Lee et al, 2013). In Ammonia spp.…”

Dibenzylideneacetones Are Potent Trypanocidal Compounds That Affect the Trypanosoma cruzi Redox System

“…A3K2A1 and A3K2A3 also led to lipid body formation, a hallmark of cellular stress that results from mitochondrial deregulation, revealed here by Nile red. The formation and fast accumulation of lipid bodies constitute a characteristic of apoptotic cell death (46,47). Other studies have reported an increase in lipid body formation in trypanosomatids under stress conditions (23,48).…”

Pathology of mitochondria in MELAS syndrome: an ultrastructural study

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