Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress. Academic Article uri icon

Overview

MeSH

  • Animals
  • Anoxia
  • DNA, Mitochondrial
  • Disease Models, Animal
  • Heme Oxygenase-1
  • Humans
  • Hyperoxia
  • Liver
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Ischemia
  • Sepsis

MeSH Major

  • Lipids
  • Mitochondria
  • Stress, Physiological

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 ( ρ 0 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.

publication date

  • 2013

has subject area

  • Animals
  • Anoxia
  • DNA, Mitochondrial
  • Disease Models, Animal
  • Heme Oxygenase-1
  • Humans
  • Hyperoxia
  • Lipids
  • Liver
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria
  • Myocardial Ischemia
  • Sepsis
  • Stress, Physiological

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3794647

Digital Object Identifier (DOI)

  • 10.1155/2013/327167

PubMed ID

  • 24175011

Additional Document Info

start page

  • 327167

volume

  • 2013