Succinate Dehydrogenase Upregulation Destabilize Complex I and Limits the Lifespan of gas-1 Mutant
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{"title"=>"Succinate Dehydrogenase Upregulation Destabilize Complex I and Limits the Lifespan of gas-1 Mutant", "type"=>"journal", "authors"=>[{"first_name"=>"Claire", "last_name"=>"Pujol", "scopus_author_id"=>"24315133900"}, {"first_name"=>"Ivana", "last_name"=>"Bratic-Hench", "scopus_author_id"=>"55316983500"}, {"first_name"=>"Marija", "last_name"=>"Sumakovic", "scopus_author_id"=>"23993167700"}, {"first_name"=>"Jürgen", "last_name"=>"Hench", "scopus_author_id"=>"26433395500"}, {"first_name"=>"Arnaud", "last_name"=>"Mourier", "scopus_author_id"=>"23467084200"}, {"first_name"=>"Linda", "last_name"=>"Baumann", "scopus_author_id"=>"55634585300"}, {"first_name"=>"Victor", "last_name"=>"Pavlenko", "scopus_author_id"=>"55634155000"}, {"first_name"=>"Aleksandra", "last_name"=>"Trifunovic", "scopus_author_id"=>"6603429548"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84875484178", "sgr"=>"84875484178", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0059493", "pmid"=>"23555681", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"368612336"}, "id"=>"36a3be2e-eb30-39bc-945a-2741e448bb72", "abstract"=>"Many Caenorhabditis elegans mutants with dysfunctional mitochondrial electron transport chain are surprisingly long lived. Both short-lived (gas-1(fc21)) and long-lived (nuo-6(qm200)) mutants of mitochondrial complex I have been identified. However, it is not clear what are the pathways determining the difference in longevity. We show that even in a short-lived gas-1(fc21) mutant, many longevity assurance pathways, shown to be important for lifespan prolongation in long-lived mutants, are active. Beside similar dependence on alternative metabolic pathways, short-lived gas-1(fc21) mutants and long-lived nuo-6(qm200) mutants also activate hypoxia-inducible factor -1α (HIF-1α) stress pathway and mitochondrial unfolded protein response (UPR(mt)). The major difference that we detected between mutants of different longevity, is in the massive loss of complex I accompanied by upregulation of complex II levels, only in short-lived, gas-1(fc21) mutant. We show that high levels of complex II negatively regulate longevity in gas-1(fc21) mutant by decreasing the stability of complex I. Furthermore, our results demonstrate that increase in complex I stability, improves mitochondrial function and decreases mitochondrial stress, putting it inside a \"window\" of mitochondrial dysfunction that allows lifespan prolongation.", "link"=>"http://www.mendeley.com/research/succinate-dehydrogenase-upregulation-destabilize-complex-i-limits-lifespan-gas1-mutant", "reader_count"=>38, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>12, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>2, "Student > Master"=>8, "Other"=>2, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>29, "Medicine and Dentistry"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>29}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}}, "reader_count_by_country"=>{"Czech Republic"=>1, "France"=>1, "Spain"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1001267"], "description"=>"<p><b>A</b> Lifespan analysis of <i>gas-1(fc21)</i> (white square) and <i>nuo-6(qm200)</i> (black cross) mutants in comparison to wild type (N2, black line) animals. <b>B</b> Analysis of mitochondrial complexes in <i>gas-1(fc21)</i> mutant. Mitochondrial proteins isolated from mouse liver (M. musculus); wild type worms (N2) or <i>gas-1(fc21)</i> mutant were separated on n-dodecyl-β-D-maltoside-based BN-PAGE. The gel was stained with Coomassie Brilliant Blue R-250 solution. <b>C</b> Analysis of mitochondrial supercomplexes in Mit mutants. Mitochondrial proteins isolated from wild type worms (N2); <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> mutants were separated on digitonin-based BN-PAGE Gels were stained and <i>in gel</i> complex I activity was determined as in B. Detection of the respiratory complexes and supercomplexes obtained after BN-PAGE by western blot using specific antibodies against complex I (CO I) and V (CO V).</p>", "links"=>[], "tags"=>["mitochondrial"], "article_id"=>662696, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Low_levels_of_mitochondrial_complex_I_in_gas_1_fc21_mutant_/662696", "title"=>"Low levels of mitochondrial complex I in <i>gas-1(fc21)</i> mutant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 15:01:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001268"], "description"=>"<p><b>A</b> Expression profiles of genes involved in various metabolic pathways: TCA cycle with malate dehydrogenase (<i>mdh-2</i>), anaerobic pathways with malic enzyme (<i>men-1</i>), glycolysis with fructose 1,6 bisphosphate aldolase (<i>aldo-1</i>), glyoxylate cycle with isocitrate lyase/malate synthase (<i>icl-1</i>). N2 (black bar), gas-1(fc21) (white bar) and nuo-6(qm200) (grey bar) animals were collected at day 1 of adulthood from synchronized populations. Bars represent relative abundance compared to control; means ± SEM. Asterisks indicate statistical significance in comparison to N2 (Student’s t-test, (*p<0.05, **p<0.01, ***p<0.0001, ****p<0.00001; n = 4). <b>B–D</b>. Effect of RNAi knockdown of <i>aldo-1</i> and <i>icl-1</i> on lifespan in (<b>B</b>) with wild type (N2); (<b>C</b>) <i>gas-1(fc21) and</i> (<b>D</b>) <i>nuo-6(qm200)</i> worms.</p>", "links"=>[], "tags"=>["long-lived", "mutants"], "article_id"=>662697, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Short_and_long_lived_complex_I_mutants_have_similar_changes_in_metabolism_/662697", "title"=>"Short and long-lived complex I mutants have similar changes in metabolism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 15:01:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001270"], "description"=>"<p><b>A</b> Relative <i>sdhb-1</i> transcript levels in wild type (N2), <i>gas-1(fc21) and nuo-6(qm200)</i> animals at L4 larval stage (L4) and day 1 (D1) of the adulthood. The bars represent means ± SEM. Asterisks indicate statistical significance in comparison to N2 worms in the control conditions (Student’s t-test, *p<0.05, n = 5). <b>B</b> Relative mitochondrial DNA levels in <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> animals compared to wild type (dashed line) with or without <i>sdhb-1</i> RNAi. The bars represent mean ± SEM. (n = 6–8) Asterisks indicate statistical significance in comparison to wild type worms in the control conditions (Student’s t-test, *p<0.05; n = 6–8). <b>C–E</b> Effect of RNAi knockdown of <i>sdhb-1</i> gene on the lifespan of (<b>C</b>) wild type (N2); (<b>D</b>) <i>nuo-6(qm200)</i> and (<b>E</b>) <i>gas-1(fc21)</i> mutants.</p>", "links"=>[], "tags"=>["ii", "negatively", "regulates", "lifespan"], "article_id"=>662699, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Complex_II_negatively_regulates_lifespan_in_gas_1_fc21_mutant_/662699", "title"=>"Complex II negatively regulates lifespan in <i>gas-1(fc21)</i> mutant.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 15:02:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001271"], "description"=>"<p><b>A</b> Relative abundance of carbonylated proteins in total or mitochondrial extract isolated from wild type (N2), <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> animals (n = 4–5). <b>B–C</b> SOD transcript and protein levels measured by (<b>B</b>) quantitative real-time RT-PCR and (<b>C)</b> Western blot. The relative abundance of SOD2 protein is shown on the lower C panel. (n = 4). <b>D</b> Transcript levels of HIF-1α-responsive genes <i>nhr-57</i> and <i>F22B5.4</i> in wild type (N2), <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> animals. Data were obtained from worms collected from synchronized population at day 1 of adulthood. The worms were grown either on control plates (L4440) or on <i>sdhb-1</i> RNAi plates (n = 5). In all panels bars represent mean ± SEM. Asterisks indicate statistical significance in comparison to wild type worms in the control conditions (Student’s t-test, *p<0.05, **p<0.01; ***p<0.001).</p>", "links"=>[], "tags"=>["mediates", "longevity", "independently", "ros", "activation", "hif-1"], "article_id"=>662700, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sdhb_1_mediates_gas_1_fc21_longevity_independently_of_ROS_production_and_or_activation_of_Hif_1_pathway_/662700", "title"=>"<i>Sdhb-1</i> mediates <i>gas-1(fc21)</i> longevity independently of ROS production and/or activation of Hif-1 pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 15:02:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001272"], "description"=>"<p><b>A</b> Analysis of mitochondrial supercomplexes in wild type worms (N2); <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> mutants grown either on control plates (L4440) or on <i>sdhb-1</i> RNAi plates (n = 5). Mitochondrial proteins were separated on digitonin-based BN-PAGE. Detection of the respiratory complexes and supercomplexes obtained after BN-PAGE by western blot using specific antibodies against complex I (CO I) and V (CO V). <b>B</b> and <b>C </b><i>In gel</i> analysis of NADH dehydrigenase and Cytochrome c Oxidase activity was performed after BN-PAGE to reveal the level of active complex I and IV, respectively by using (<b>B</b>) <i>gas-1(fc21)</i> and (<b>C</b>) <i>nuo-6(qm200)</i> animals. <b>D</b> Oxygen consumption of wild type worms (N2); <i>gas-1(fc21)</i> and <i>nuo-6(qm200)</i> animals subjected to RNAi against <i>sdhb-1</i> at day 1 of adulthood. The bars represent means ± SEM. Asterisks indicate statistical significance in comparison to N2 worms in the control conditions (Student’s t-test, *p<0.05, **p<0.01, n = 5).</p>", "links"=>[], "tags"=>["stabilizes", "co"], "article_id"=>662701, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sdhb_1_silencing_stabilizes_CO_I_levels_in_gas_1_fc21_mutant_/662701", "title"=>"<i>Sdhb-1</i> silencing stabilizes CO I levels in <i>gas-1(fc21) mutant.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-29 15:03:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001274", "https://ndownloader.figshare.com/files/1001275", "https://ndownloader.figshare.com/files/1001276", "https://ndownloader.figshare.com/files/1001278", "https://ndownloader.figshare.com/files/1001279", "https://ndownloader.figshare.com/files/1001281"], "description"=>"<div><p>Many <i>Caenorhabditis elegans</i> mutants with dysfunctional mitochondrial electron transport chain are surprisingly long lived. Both short-lived (<i>gas-1(fc21)</i>) and long-lived (<i>nuo-6(qm200)</i>) mutants of mitochondrial complex I have been identified. However, it is not clear what are the pathways determining the difference in longevity. We show that even in a short-lived <i>gas-1(fc21)</i> mutant, many longevity assurance pathways, shown to be important for lifespan prolongation in long-lived mutants, are active. Beside similar dependence on alternative metabolic pathways, short-lived <i>gas-1(fc21)</i> mutants and long-lived <i>nuo-6(qm200)</i> mutants also activate hypoxia-inducible factor –1α (HIF-1α) stress pathway and mitochondrial unfolded protein response (UPR<sup>mt</sup>). The major difference that we detected between mutants of different longevity, is in the massive loss of complex I accompanied by upregulation of complex II levels, only in short-lived, <i>gas-1(fc21)</i> mutant. We show that high levels of complex II negatively regulate longevity in <i>gas-1(fc21)</i> mutant by decreasing the stability of complex I. Furthermore, our results demonstrate that increase in complex I stability, improves mitochondrial function and decreases mitochondrial stress, putting it inside a “window” of mitochondrial dysfunction that allows lifespan prolongation.</p> </div>", "links"=>[], "tags"=>["succinate", "dehydrogenase", "upregulation", "destabilize", "limits", "lifespan", "mutant"], "article_id"=>662703, "categories"=>["Physiology", "Developmental Biology", "Cell Biology", "Biotechnology", "Evolutionary Biology"], "users"=>["Claire Pujol", "Ivana Bratic-Hench", "Marija Sumakovic", "Jürgen Hench", "Arnaud Mourier", "Linda Baumann", "Victor Pavlenko", "Aleksandra Trifunović"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059493.s001", "https://dx.doi.org/10.1371/journal.pone.0059493.s002", "https://dx.doi.org/10.1371/journal.pone.0059493.s003", "https://dx.doi.org/10.1371/journal.pone.0059493.s004", "https://dx.doi.org/10.1371/journal.pone.0059493.s005", "https://dx.doi.org/10.1371/journal.pone.0059493.s006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Succinate_Dehydrogenase_Upregulation_Destabilize_Complex_I_and_Limits_the_Lifespan_of_gas_1_Mutant/662703", "title"=>"Succinate Dehydrogenase Upregulation Destabilize Complex I and Limits the Lifespan of <i>gas-1</i> Mutant", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-29 15:04:12"}

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Relative Metric

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