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Article
Mitochondria in energy-limited states: mechanisms that blunt the signaling of cell death
Journal of Experimental Biology (2008)
  • Steven C. Hand
  • Michael A Menze, University of Louisville
Abstract
Cellular conditions experienced during energy-limited states – elevated calcium, shifts in cellular adenylate status, compromised mitochondrial membrane potential – are precisely those that trigger, at least in mammals, the mitochondrion to initiate opening of the permeability transition pore, to assemble additional protein release channels, and to release pro-apoptotic factors. These proapototic factors in turn activate initiator and executer caspases. How is activation of mitochondria-based pathways for the signaling of apoptotic and necrotic cell death avoided under conditions of hypoxia, anoxia, diapause, estivation and anhydrobiosis? Functional trade-offs in environmental tolerance may have occurred in parallel with the evolution of diversified pathways for the signaling of cell death in eukaryotic organisms. Embryos of the brine shrimp, Artemia franciscana, survive extended periods of anoxia and diapause, and evidence indicates that opening of the mitochondrial permeability transition pore and release of cytochrome c (cyt-c) do not occur. Further, caspase activation in this crustacean is not dependent on cyt-c. Its caspases display regulation by nucleotides that is consistent with ʻapplying the brakesʼ to cell death during energy limitation. Unraveling the mechanisms by which organisms in extreme environments avoid cell death may suggest possible interventions during disease states and biostabilization of mammalian cells.
Keywords
  • apoptosis,
  • necrosis,
  • permeability transition pore,
  • metabolic depression,
  • anoxia,
  • diapause,
  • caspase activation
Disciplines
Publication Date
2008
Publisher Statement
This research is available in open access full text at http://jeb.biologists.org/content/211/12/1829.full.pdf+html. doi: 10.1242/​jeb.000299
Citation Information
Steven C. Hand and Michael A Menze. "Mitochondria in energy-limited states: mechanisms that blunt the signaling of cell death" Journal of Experimental Biology Vol. 211 Iss. 12 (2008)
Available at: http://works.bepress.com/michael_menze/12/