Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans

Title: Anthranilate fluorescence marks a calcium-propagated necrotic wave that promotes organismal death in C. elegans
Authors: Coburn, C
Allman, E
Mahanti, P
Benedetto, A
Cabreiro, F
Pincus, Z
Matthijssens, F
Araiz, C
Mandel, A
Vlachos, M
Edwards, S-A
Fischer, G
Davidson, A
Pryor, RE
Stevens, A
Slack, FJ
Tavernarakis, N
Braeckman, BP
Schroeder, FC
Nehrke, K
Gems, D
Item Type: Journal Article
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.
Issue Date: 23-Jul-2013
Date of Acceptance: 13-Jun-2013
URI: http://hdl.handle.net/10044/1/73527
DOI: https://doi.org/10.1371/journal.pbio.1001613
ISSN: 1544-9173
Publisher: Public Library of Science (PLoS)
Start Page: 1
End Page: 17
Journal / Book Title: PLoS Biology
Volume: 11
Issue: 7
Copyright Statement: © 2013 Coburn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
CELL-DEATH
CAENORHABDITIS-ELEGANS
OXIDATIVE STRESS
RHYTHMIC BEHAVIOR
GENETIC-ANALYSIS
NEURONAL DEATH
GAP-JUNCTIONS
NECROSIS
ACID
LIPOFUSCIN
Animals
Caenorhabditis elegans
Esters
Fluorescence
Oxidative Stress
ortho-Aminobenzoates
Animals
Caenorhabditis elegans
Esters
Oxidative Stress
Fluorescence
ortho-Aminobenzoates
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
CELL-DEATH
CAENORHABDITIS-ELEGANS
OXIDATIVE STRESS
RHYTHMIC BEHAVIOR
GENETIC-ANALYSIS
NEURONAL DEATH
GAP-JUNCTIONS
NECROSIS
ACID
LIPOFUSCIN
Developmental Biology
06 Biological Sciences
11 Medical and Health Sciences
07 Agricultural and Veterinary Sciences
Publication Status: Published
Article Number: ARTN e1001613
Online Publication Date: 2013-07-23
Appears in Collections:Clinical Sciences
Molecular Sciences



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