The mysterious case of the c. elegans gut granule: Death anthranilic acid and the kynurenine pathway

Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London London, UK.
Frontiers in Genetics 08/2013; 4:151. DOI: 10.3389/fgene.2013.00151
Source: PubMed


Gut granules are lysosome-like organelles with acidic interiors that are found in large numbers within the intestine of the nematode Caenorhabditis elegans. They are particularly prominent when viewed under ultraviolet light, which causes them to emit intense blue fluorescence. Yet the function of these large and abundant organelles in this heavily-studied model organism remains unclear. One possibility is that they serve as storage organelles, for example of zinc. A new clue to gut granule function is the identification of the blue fluorescent material that they contain as a glycosylated form of anthranilic acid, which is derived from tryptophan by action of the kynurenine pathway. This compound can also serve a surprising role as a natural, endogenous marker of organismal death.

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    • "The gut granule fluorescence lipofuscin, a complex molecular waste production that accumulates within lysosomes in aging mammalian cells and lipofuscin can contain Schiff bases, which are having similar spectral similarities to the worm blue fluorescence. Consistent with this, blue fluorescence levels increase in aging worm populations[9]. C. elegans hermaphrodites are demonstrated to display agerelated accumulation of fluorescent material characterized by an excitation maximum of about 340nm and an emission maximum of about 430nm. The fact that significant changes in nematode age pigment accumulation can be demonstrated within weeks provides a clear rationale for the use of nematodes to study this phenomenon. "

    Preview · Article · Nov 2015
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    • "New facts are needed to advance our understanding of aging, and studies of model organisms continue to provide us with valuable information. There are five articles in the collection, which represent new discoveries in genetics of aging of Caenorhabditis elegans (Bharill et al., 2013; Coburn and Gems, 2013), Drosophila melanogaster (Rogina and Helfand, 2013; Shostal and Moskalev, 2013), and mice (Bartke and Westbrook, 2012). In one of the most intriguing articles, Coburn and Gems (2013) come to the conclusion that the blue fluorescence of gut granules, a marker of death in C. elegans, is issued from anthranilic acid glucosyl esters, rather than from lipofuscin. "

    Full-text · Article · Aug 2014 · Frontiers in Genetics
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    ABSTRACT: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist. In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease.
    Full-text · Article · Oct 2014 · Frontiers in Immunology
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