title: Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans.
abstract: Oxygen is an absolute requirement for multicellular life. Animals that are deprived of oxygen for sufficient periods of time eventually become injured and die. This is largely due to the fact that, without oxygen, animals are unable to generate sufficient quantities of energy. In human diseases triggered by oxygen deprivation, such as heart attack and stroke, hyposmotic stress and cell swelling (edema) arise in affected tissues as a direct result of energetic failure. Edema independently enhances tissue injury in these diseases by incompletely understood mechanisms, resulting in poor clinical outcomes. Here, we present investigations into the effects of osmotic stress during complete oxygen deprivation (anoxia) in the genetically tractable nematode Caenorhabditis elegans. Our findings demonstrate that nematode survival of a hyposmotic environment during anoxia (hyposmotic anoxia) depends on the nematode's ability to engage in glycogen metabolism. We also present results of a genome-wide screen for genes affecting glycogen content and localization in the nematode, showing that nematode survival of hyposmotic anoxia depends on a large number of these genes. Finally, we show that an inability to engage in glycogen synthesis results in suppression of the enhanced survival phenotype observed in daf-2 insulin-like pathway mutants, suggesting that alterations in glycogen metabolism may serve as a basis for these mutants' resistance to hyposmotic anoxia.
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195 Medical Scientist Training Program, University of Washington, Seattle, Washington 98195 Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: John C
authors.identifier: http://orcid.org/0000-0003-4754-5828
authors.initials: JC
authors.lastname: LaMacchia
authors.affiliation: Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195 Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Harold N
authors.initials: HN
authors.lastname: Frazier
authors.affiliation: Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 mroth@fredhutch.org.
authors.forename: Mark B
authors.identifier: http://orcid.org/0000-0002-6535-3611
authors.initials: MB
authors.lastname: Roth
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism*; D009154:Mutation; D009997:Osmotic Pressure; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D006003:Glycogen; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
keywords: C. elegans; anoxia; glycogen; insulin signaling; osmotic stress