Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans
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{"title"=>"Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans", "type"=>"journal", "authors"=>[{"first_name"=>"Cassandra", "last_name"=>"Coburn", "scopus_author_id"=>"55808589500"}, {"first_name"=>"Erik", "last_name"=>"Allman", "scopus_author_id"=>"35241750200"}, {"first_name"=>"Parag", "last_name"=>"Mahanti", "scopus_author_id"=>"37077711400"}, {"first_name"=>"Alexandre", "last_name"=>"Benedetto", "scopus_author_id"=>"25822166900"}, {"first_name"=>"Filipe", "last_name"=>"Cabreiro", "scopus_author_id"=>"24474163400"}, {"first_name"=>"Zachary", "last_name"=>"Pincus", "scopus_author_id"=>"10339920500"}, {"first_name"=>"Filip", "last_name"=>"Matthijssens", "scopus_author_id"=>"6505969845"}, {"first_name"=>"Caroline", "last_name"=>"Araiz", "scopus_author_id"=>"8147650100"}, {"first_name"=>"Abraham", "last_name"=>"Mandel", "scopus_author_id"=>"55808151600"}, {"first_name"=>"Manolis", "last_name"=>"Vlachos", "scopus_author_id"=>"35724987300"}, {"first_name"=>"Sally Anne", "last_name"=>"Edwards", "scopus_author_id"=>"55608611800"}, {"first_name"=>"Grahame", "last_name"=>"Fischer", "scopus_author_id"=>"55808668600"}, {"first_name"=>"Alexander", "last_name"=>"Davidson", "scopus_author_id"=>"57198074398"}, {"first_name"=>"Rosina E.", "last_name"=>"Pryor", "scopus_author_id"=>"56053966200"}, {"first_name"=>"Ailsa", "last_name"=>"Stevens", "scopus_author_id"=>"55808236700"}, {"first_name"=>"Frank J.", "last_name"=>"Slack", "scopus_author_id"=>"7004379704"}, {"first_name"=>"Nektarios", "last_name"=>"Tavernarakis", "scopus_author_id"=>"20035582600"}, {"first_name"=>"Bart P.", "last_name"=>"Braeckman", "scopus_author_id"=>"6701332641"}, {"first_name"=>"Frank C.", "last_name"=>"Schroeder", "scopus_author_id"=>"8342418700"}, {"first_name"=>"Keith", "last_name"=>"Nehrke", "scopus_author_id"=>"7003836880"}, {"first_name"=>"David", "last_name"=>"Gems", "scopus_author_id"=>"7003303767"}], "year"=>2013, "source"=>"PLoS Biology", "identifiers"=>{"pmid"=>"23935448", "doi"=>"10.1371/journal.pbio.1001613", "sgr"=>"84880930694", "isbn"=>"1545-7885 (Electronic) 1544-9173 (Linking)", "scopus"=>"2-s2.0-84880930694", "issn"=>"15449173", "pui"=>"369462999"}, "id"=>"80a6c4c6-1c47-3db9-9f03-f4e4b7203c09", "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.", "link"=>"http://www.mendeley.com/research/anthranilate-fluorescence-marks-calciumpropagated-necrotic-wave-promotes-organismal-death-c-elegans", "reader_count"=>196, "reader_count_by_academic_status"=>{"Unspecified"=>7, "Professor > Associate Professor"=>10, "Researcher"=>39, "Student > Doctoral Student"=>10, "Student > Ph. D. 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Student"=>57, "Student > Postgraduate"=>4, "Student > Master"=>29, "Other"=>7, "Student > Bachelor"=>23, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>2, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Agricultural and Biological Sciences"=>118, "Chemistry"=>5, "Computer Science"=>2, "Earth and Planetary Sciences"=>1, "Engineering"=>7, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>21, "Materials Science"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>13, "Neuroscience"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>8, "Psychology"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>8}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>7}, "Chemistry"=>{"Chemistry"=>5}, "Neuroscience"=>{"Neuroscience"=>5}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>118}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>21}}, "reader_count_by_country"=>{"United States"=>7, "Japan"=>3, "United Kingdom"=>5, "Israel"=>1, "Nigeria"=>1, "Lithuania"=>1, "France"=>3, "Germany"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1126664"], "description"=>"<p>(A, B) Fluorescent gut granules (arrow heads) in intestinal cells of healthy, young adult <i>C. elegans</i>. Bar, 50 µm. (C–F) Hyperoxia (5-d exposure) and free iron (1-d exposure) increase protein oxidation but not blue fluorescence, mean of 3 biological replicates ± SEM, * <i>p</i><0.05, ** <i>p</i><0.01.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms"], "article_id"=>751695, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g001", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Molecular_damage_does_not_increase_blue_fluorescence_/751695", "title"=>"Molecular damage does not increase blue fluorescence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126665"], "description"=>"<p>(A) Fluorescence levels in individual animals (a–e) during life and death. (B) Typical fluorescence change during death from old age. 0 h, cessation of movement (death). All six images are of the same dying animal. Scale bar, 50 µm. (C) Mean levels of fluorescence relative to time of death (black line), ± SD (blue lines). Data from 47 individuals. Inset, death peak detail. AU, arbitrary units.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "fluorescence"], "article_id"=>751696, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g002", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Blue_fluorescence_increases_with_death_/751696", "title"=>"Blue fluorescence increases with death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126666"], "description"=>"<p>(A) DF induced by hot pick killing in young WT adult (<i>N</i> = 87), L4 (<i>N</i> = 26), and male <i>C. elegans</i> (<i>N</i> = 25), and in other nematode species <i>C. briggsae</i> (<i>N</i> = 26) and <i>P. pacificus</i> (<i>N</i> = 49). ± SD, ***<i>p</i><0.001. L4 larvae and adult males show smaller increases in DF than adult hermaphrodites, perhaps due to their smaller size. (B) Typical fluorescence increase in young adult worm killed by a hot pick. (C) Fluorescence increases in an anterior to posterior wave. Figure shows mean fluorescence intensity (values normalized to highest value in each individual) at 5 points along the intestine of animals dying of old age (<i>N</i> = 29). Due to individual variation (range, 1 h 55 min–5 h 30 min, mean ∼3 h), the duration of each observation was divided into 5 equal points for measurement. T = 0 is the point at which time-lapse photography of dying (late stage C) worms was initiated. (D) DF will not propagate in a posterior to anterior wave. Head, int1 and int2 anterior intestinal cells; tail, int9 posterior intestinal cells.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms"], "article_id"=>751697, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_DF_/751697", "title"=>"Characteristics of DF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126667"], "description"=>"<p>(A) Compounds down-regulated in <i>glo-1(zu437)</i> background. (B) Anthranilic acid (AA) is derived from tryptophan via the kynurenine pathway. angl#1 and angl#2 may result from action of glucosyltransferases. (C and D) RNAi of putative tryptophan 2,3-dioxygenase (C28H8.11) significantly reduces both gut granule and DF. Bar, 100 µm, error bars ± SD. Negative fluorescence shown by error bars are due to normalization via subtraction of background fluorescence.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "generated", "kynurenine"], "article_id"=>751698, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g004", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DF_is_generated_by_the_kynurenine_pathway_/751698", "title"=>"DF is generated by the kynurenine pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126669"], "description"=>"<p>(A) The calpain-cathepsin necrosis cascade. (B) Effects of inhibition of necrosis on DF, in ER calcium mutants, a calpain mutant, lysosomal acidosis mutants, cathepsin mutants, and an innexin mutant. Death was induced by freeze-thaw in young adults. Plots in (B) and (C) show mean ± SD, *<i>p</i><0.05, **<i>p</i><0.01 and ***<i>p</i><0.001. Statistics: Wild type, <i>N</i> = 7 independent assays (different days), 50 worms/assay <i>n</i> = 350; <i>asp-4</i>, <i>N</i> = 7, <i>n</i> = 350, <i>p</i><0.001; <i>crt-1</i>, <i>N</i> = 3, <i>n</i> = 150, <i>p</i><0.01; <i>unc-68</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i><0.001; <i>itr-1</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i><0.01; <i>tra-3</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i><0.001; <i>vha-12</i>, <i>N</i> = 7, <i>n</i> = 350, <i>p</i>>0.05; <i>unc-32</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i>>0.05; <i>cad-1</i>, <i>N</i> = 7, <i>n</i> = 350, <i>p</i><0.001; <i>inx-16</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i><0.001. (C) Most necrosis mutants are significantly more resistant to death induced by osmotic stress (500 mM NaCl). Wild type, <i>N</i> = 6, <i>n</i> = 300; <i>asp-4</i>, <i>N</i> = 7, <i>n</i> = 350, <i>p</i>>0.05; <i>crt-1</i>, <i>N</i> = 5, <i>n</i> = 250, <i>p</i>>0.05; <i>unc-68</i>, <i>N</i> = 2, <i>n</i> = 150, <i>p</i>>0.05; <i>itr-1</i>, <i>N</i> = 3, <i>n</i> = 300, <i>p</i><0.001; <i>tra-3</i>, <i>N</i> = 3, <i>n</i> = 100, <i>p</i><0.01; <i>vha-12</i>, <i>N</i> = 3, <i>n</i> = 150, <i>p</i>>0.05; <i>unc-32</i>, <i>N</i> = 2, <i>n</i> = 100, <i>p</i><0.05; <i>cad-1</i>, <i>N</i> = 6, <i>n</i> = 300, <i>p</i><0.001; <i>inx-16</i>, <i>N</i> = 4, <i>n</i> = 200, <i>p</i><0.001.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "necrosis", "pathway"], "article_id"=>751699, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g005", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_necrosis_pathway_reduces_DF_/751699", "title"=>"Inhibition of necrosis pathway reduces DF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126670"], "description"=>"<p>(A and B) <i>inx-16(ox144)</i> reduces DF and prevents its propagation (death induced using heated wire). (C–E) Ca<sup>2+</sup> levels and pH in the intestine of worms killed by oxidative stress (<i>t</i>-BOOH). (C) <i>In vivo</i> Ca<sup>2+</sup> levels rise at death in the anterior intestine prior to the posterior intestine, consistent with an anterior to posterior Ca<sup>2+</sup> wave. Mean ± SD. (D) The Ca<sup>2+</sup> reporter expressed in an <i>inx-16(ox144)</i> strain confirms that Ca<sup>2+</sup>, like DF, rises in the anterior but does not spread. Mean ± SD. (E) <i>In vivo</i> pH decreases at death from pH ∼7.35 to ∼6.6 in the anterior intestine prior to the posterior intestine, consistent with an anterior to posterior wave of cytosolic acidosis. Mean ± SD. In (C–E), “anterior” indicates the int1 and int2 anterior intestinal cells, and “posterior” the int9 posterior intestinal cells.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "df", "accompanied", "cytosolic"], "article_id"=>751700, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g006", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_spread_of_DF_is_dependent_on_calcium_and_is_accompanied_by_cytosolic_acidosis_/751700", "title"=>"The spread of DF is dependent on calcium, and is accompanied by cytosolic acidosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126671"], "description"=>"<p>(A) Wave of blue fluorescence is accompanied by loss of lysosomal membrane integrity upon killing with <i>t</i>-BOOH. The quenching of uranin fluorescence at low pH makes it an excellent marker for loss of membrane integrity in lysosome-related organelles. (B) Working model of DF and systemic necrosis during organismal death in <i>C. elegans</i>. Unidentified factors (possibly calcium influx) trigger an initial necrotic event, typically in the anterior intestinal cells. This necrotic event includes cytosolic acidosis and LMP, which is associated with a burst of blue fluorescence from anthranilic acid glucosyl esters, which render visible the occurrence of necrosis. Necrosis in the anterior cell leads to calcium influx into the neighboring cells via INX-16 channels, triggering further necrotic events, and a cascade of necrosis along the intestine. In stress-induced death, but not aging-induced death, systemic necrosis can detectably hasten organismal death. However, it also seems likely that necrotic destruction of the intestine, a major organ within <i>C. elegans</i>, contributes to organismal death in senescent nematodes.</p>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "necrosis", "mutants", "organismal"], "article_id"=>751701, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001613.g007", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stress_resistance_of_necrosis_mutants_suggest_model_for_organismal_death_/751701", "title"=>"Stress resistance of necrosis mutants suggest model for organismal death.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-23 01:50:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1126682", "https://ndownloader.figshare.com/files/1126685", "https://ndownloader.figshare.com/files/1126686", "https://ndownloader.figshare.com/files/1126691", "https://ndownloader.figshare.com/files/1126695", "https://ndownloader.figshare.com/files/1126698", "https://ndownloader.figshare.com/files/1126701", "https://ndownloader.figshare.com/files/1126712", "https://ndownloader.figshare.com/files/1126724", "https://ndownloader.figshare.com/files/1126725", "https://ndownloader.figshare.com/files/1126727", "https://ndownloader.figshare.com/files/1126732", "https://ndownloader.figshare.com/files/1126737", "https://ndownloader.figshare.com/files/1126742", "https://ndownloader.figshare.com/files/1126747", "https://ndownloader.figshare.com/files/1126753", "https://ndownloader.figshare.com/files/1126754", "https://ndownloader.figshare.com/files/1126755", "https://ndownloader.figshare.com/files/1126756", "https://ndownloader.figshare.com/files/1126758", "https://ndownloader.figshare.com/files/1126761", "https://ndownloader.figshare.com/files/1126763", "https://ndownloader.figshare.com/files/1126771", "https://ndownloader.figshare.com/files/1126772", "https://ndownloader.figshare.com/files/1126773", "https://ndownloader.figshare.com/files/1126774", "https://ndownloader.figshare.com/files/1126775", "https://ndownloader.figshare.com/files/1126776"], "description"=>"<div><p>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 <i>Caenorhabditis elegans</i>. 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 <i>C. elegans</i> 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 <i>C. elegans</i> organismal death.</p></div>", "links"=>[], "tags"=>["genetics", "microbiology", "Model organisms", "anthranilate", "fluorescence", "marks", "calcium-propagated", "necrotic", "organismal"], "article_id"=>751704, "categories"=>["Biological Sciences"], "users"=>["Cassandra Coburn", "Erik Allman", "Parag Mahanti", "Alexandre Benedetto", "Filipe Cabreiro", "Zachary Pincus", "Filip Matthijssens", "Caroline Araiz", "Abraham Mandel", "Manolis Vlachos", "Sally-Anne Edwards", "Grahame Fischer", "Alexander Davidson", "Rosina E. Pryor", "Ailsa Stevens", "Frank J. Slack", "Nektarios Tavernarakis", "Bart P. Braeckman", "Frank C. Schroeder", "Keith Nehrke", "David Gems"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001613.s001", "https://dx.doi.org/10.1371/journal.pbio.1001613.s002", "https://dx.doi.org/10.1371/journal.pbio.1001613.s003", "https://dx.doi.org/10.1371/journal.pbio.1001613.s004", "https://dx.doi.org/10.1371/journal.pbio.1001613.s005", "https://dx.doi.org/10.1371/journal.pbio.1001613.s006", "https://dx.doi.org/10.1371/journal.pbio.1001613.s007", "https://dx.doi.org/10.1371/journal.pbio.1001613.s008", "https://dx.doi.org/10.1371/journal.pbio.1001613.s009", "https://dx.doi.org/10.1371/journal.pbio.1001613.s010", "https://dx.doi.org/10.1371/journal.pbio.1001613.s011", "https://dx.doi.org/10.1371/journal.pbio.1001613.s012", "https://dx.doi.org/10.1371/journal.pbio.1001613.s013", "https://dx.doi.org/10.1371/journal.pbio.1001613.s014", "https://dx.doi.org/10.1371/journal.pbio.1001613.s015", "https://dx.doi.org/10.1371/journal.pbio.1001613.s016", "https://dx.doi.org/10.1371/journal.pbio.1001613.s017", "https://dx.doi.org/10.1371/journal.pbio.1001613.s018", "https://dx.doi.org/10.1371/journal.pbio.1001613.s019", "https://dx.doi.org/10.1371/journal.pbio.1001613.s020", "https://dx.doi.org/10.1371/journal.pbio.1001613.s021", "https://dx.doi.org/10.1371/journal.pbio.1001613.s022", "https://dx.doi.org/10.1371/journal.pbio.1001613.s023", "https://dx.doi.org/10.1371/journal.pbio.1001613.s024", "https://dx.doi.org/10.1371/journal.pbio.1001613.s025", "https://dx.doi.org/10.1371/journal.pbio.1001613.s026", "https://dx.doi.org/10.1371/journal.pbio.1001613.s027", "https://dx.doi.org/10.1371/journal.pbio.1001613.s028"], "stats"=>{"downloads"=>107, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Anthranilate_Fluorescence_Marks_a_Calcium_Propagated_Necrotic_Wave_That_Promotes_Organismal_Death_in_C_elegans_/751704", "title"=>"Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in <i>C. elegans</i>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-23 01:50:12"}

PMC Usage Stats | Further Information

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Relative Metric

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