title: Apoptosis-induced mitochondrial dysfunction causes cytoplasmic lipid droplet formation.
abstract: A characteristic of apoptosis is the rapid accumulation of cytoplasmic lipid droplets, which are composed largely of neutral lipids. The proton signals from these lipids have been used for the non-invasive detection of cell death using magnetic resonance spectroscopy. We show here that despite an apoptosis-induced decrease in the levels and activities of enzymes involved in lipogenesis, which occurs downstream of p53 activation and inhibition of the mTOR signaling pathway, the increase in lipid accumulation is due to increased de novo lipid synthesis. This results from inhibition of mitochondrial fatty acid β-oxidation, which coupled with an increase in acyl-CoA synthetase activity, diverts fatty acids away from oxidation and into lipid synthesis. The inhibition of fatty acid oxidation can be explained by a rapid rise in mitochondrial membrane potential and an attendant increase in the levels of reactive oxygen species.
authors.affiliation: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Boren
authors.forename: K M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D005227:Fatty Acids; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D003066:Coenzyme A Ligases