Glycogen Fuels Survival During Hyposmotic-Anoxic Stress in Caenorhabditis elegans

• Published in: Genetics (Austin) Vol. 201; no. 1; pp. 65 - 74
• Main Authors: LaMacchia, John C, Frazier, 3rd, Harold N, Roth, Mark B
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.09.2015
• Subjects: Animals; Caenorhabditis; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Hypoxia; Disease; Gene Expression Regulation; Glycogen - metabolism; Investigations; Metabolism; Mutation; Nematoda; Osmotic Pressure; Oxygen; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; osmotic stress; C. elegans; insulin signaling; glycogen; anoxia
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.115.179416

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.