NDLI: Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans

Content Provider	PubMed Central
Author	Coburn, Cassandra Allman, Erik Parag, Mahanti Benedetto, Alexandre Filipe, Cabreiro Pincus, Zachary Filip, Matthijssens Araiz, Caroline Mandel, Abraham Vlachos, Manolis Edwards, Sally-anne Fischer, Grahame Davidson, Alexander Pryor, Rosina E. Stevens, Ailsa Slack, Frank J. Tavernarakis, Nektarios Braeckman, Bart P. Schroeder, Frank C. Keith, Nehrke Gems, David
Editor	Green, Douglas R.
Copyright Year	2013
Abstract	For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters—not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals—e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death.
Related Links	http://dx.doi.org/10.1371/journal.pbio.1001613
Starting Page	1001613
File Format	PDF
ISSN	15457885
e-ISSN	15457885
Journal	PLoS Biology
Issue Number	7
Volume Number	11
Language	English
Publisher	Public Library of Science
Publisher Date	2013-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Agricultural and Biological Sciences(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Biochemistry, Genetics and Molecular Biology Agricultural and Biological Sciences

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