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Cited by 166Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyAutophagy in Disease and Therapy

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A Regulated Response to Impaired Respiration Slows Behavioral Rates and Increases Lifespan in Caenorhabditis elegans

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Cristina, David, Cary, Michael, Lunceford, Adam, Clarke, Catherine, Kenyon, Cynthia·2009·PLoS Genetics
DOI 10.1371/journal.pgen.1000450PMC PMC2660839
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Abstract

When mitochondrial respiration or ubiquinone production is inhibited in Caenorhabditis elegans, behavioral rates are slowed and lifespan is extended. Here, we show that these perturbations increase the expression of cell-protective and metabolic genes and the abundance of mitochondrial DNA. This response is similar to the response triggered by inhibiting respiration in yeast and mammalian cells, termed the "retrograde response". As in yeast, genes switched on in C. elegans mitochondrial mutants extend lifespan, suggesting an underlying evolutionary conservation of mechanism. Inhibition of fstr-1, a potential signaling gene that is up-regulated in clk-1 (ubiquinone-defective) mutants, and its close homolog fstr-2 prevents the expression of many retrograde-response genes and accelerates clk-1 behavioral and aging rates. Thus, clk-1 mutants live in "slow motion" because of a fstr-1/2-dependent pathway that responds to ubiquinone. Loss of fstr-1/2 does not suppress the phenotypes of all long-lived mitochondrial mutants. Thus, although different mitochondrial perturbations activate similar transcriptional and physiological responses, they do so in different ways.

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Figure 1 Up-regulated GO categories in worm and yeast mitochondrial mutants. Tables A and B show the p-values for the most significant GO categories found in isp-1(−), clk-1(−) and cyc-1(RNAi) animals (p<0.1; FDR<0.1 in at least one mutant) (red represents more significant, yellow represents less significant). The “yeast petite” column indicates whether each GO category found in one or more of the C. elegans mutants was also overrepresented in petite yeast data sets. GO categories are aggregated into GO “branches” (same cell in table) if they are part of the same GO hierarchy and are directly related to each other. NS represents non-significant, for GO categories that were below our cut-off. NA represents not available, for GO categories that had no annotated genes in yeast or for situations in which no expression data was available for that category. GO categories were separated into two tables (A and B). A) GO categories present in two or more C. elegans mitochondrial mutants. All overlap sets, both between different combinations of two mutants, as well as between all three mutants, are highly significant (p<0.001). In addition, the number of categories shared between all three C. elegans mutants and yeast “petites” is also much higher than expected by random chance (p<0.001; one would expect 2 categories by random chance). B) GO categories present in only one mitochondrial mutant. Categories that were present in only one mutant were also less likely to be present in the yeast petite dataset. Note that cell-protective genes are not well annotated as distinct GO classes in current C. elegans data bases (i.e., WormBase).
Figure 1 Up-regulated GO categories in worm and yeast mitochondrial mutants. Tables A and B show the p-values for the most significant GO categories found in isp-1(−), clk-1(−) and cyc-1(RNAi) animals (p<0.1; FDR<0.1 in at least one mutant) (red represents more significant, yellow represents less significant). The “yeast petite” column indicates whether each GO category found in one or more of the C. elegans mutants was also overrepresented in petite yeast data sets. GO categories are aggregated into GO “branches” (same cell in table) if they are part of the same GO hierarchy and are directly related to each other. NS represents non-significant, for GO categories that were below our cut-off. NA represents not available, for GO categories that had no annotated genes in yeast or for situations in which no expression data was available for that category. GO categories were separated into two tables (A and B). A) GO categories present in two or more C. elegans mitochondrial mutants. All overlap sets, both between different combinations of two mutants, as well as between all three mutants, are highly significant (p<0.001). In addition, the number of categories shared between all three C. elegans mutants and yeast “petites” is also much higher than expected by random chance (p<0.001; one would expect 2 categories by random chance). B) GO categories present in only one mitochondrial mutant. Categories that were present in only one mutant were also less likely to be present in the yeast petite dataset. Note that cell-protective genes are not well annotated as distinct GO classes in current C. elegans data bases (i.e., WormBase).CC BY · PubMed Central
Figure 2 Mitochondrial DNA quantification. Percent increase in total mitochondrial DNA relative to wild type is shown, as measured by qPCR. Data are shown for two different mitochondrial primer pairs across five independent biological repeats. (*) indicates significance of p<0.05 after Bonferroni multiple comparison correction. Error bars are ±SEM. clk-1(−) primer set A: m (mean) = 1.31±0.07, primer set B: m = 1.29±0.08; cyc-1(RNAi) primer set A: m = 1.07±0.03, primer set B: m = 1.08±0.03; isp-1(−) primer set A: m = 1.35±0.14, primer set B: m = 1.21±0.13.
Figure 2 Mitochondrial DNA quantification. Percent increase in total mitochondrial DNA relative to wild type is shown, as measured by qPCR. Data are shown for two different mitochondrial primer pairs across five independent biological repeats. (*) indicates significance of p<0.05 after Bonferroni multiple comparison correction. Error bars are ±SEM. clk-1(−) primer set A: m (mean) = 1.31±0.07, primer set B: m = 1.29±0.08; cyc-1(RNAi) primer set A: m = 1.07±0.03, primer set B: m = 1.08±0.03; isp-1(−) primer set A: m = 1.35±0.14, primer set B: m = 1.21±0.13.CC BY · PubMed Central
Figure 3 Lifespan measurements of long-lived mitochondrial mutants subjected to RNAi of individual retrograde-response genes. A) aqp-1 RNAi significantly decreased the lifespan extension produced by clk-1 mutations from 26% (control) to 7%; p<0.05 (left panel) and from 17% (control) to 0%; p<0.0001 (right panel). Left panel - WT subjected to control (vector-only) RNAi: N = 103, m = 13.4 days; clk-1(−) mutants subjected to control RNAi: N = 105, m = 16.9 days; clk-1(−) mutants subjected to aqp-1 RNAi: N = 105, m = 14.4 days. Right panel - WT subjected to control (vector-only) RNAi: N = 77, m = 15.1 days; clk-1(−) mutants subjected to control RNAi: N = 137, m = 17.3 days; clk-1(−) mutants subjected to aqp-1 RNAi: N = 70, m = 15.1 days. aqp-1 RNAi did not significantly affect WT lifespan (Figure S1). B) fstr-1/2 RNAi significantly decreased the lifespan extension produced by clk-1 mutation from 26% to 3%, p<0.01 (left panel) and from 17% (control) to 0%; p<0.0001 (right panel). Left panel - WT subjected to control RNAi, same as in Figure 2A; clk-1(−) mutants subjected to control RNAi, same as in Figure 2A; clk-1(−) mutants subjected to fstr-1/2 RNAi: N = 108, m = 13.8 days. Right Panel - WT subjected to control (vector-only) RNAi: N = 77, m = 15.1 days; clk-1(−) mutants subjected to control RNAi: N = 137, m = 17.3 days; clk-1(−) mutants subjected to fstr-1/2 RNAi: N = 63, m = 14.5 days. fstr-1/2 RNAi did not significantly affect WT lifespan (Figure S1). C) cdr-2 RNAi suppressed the longevity increase produced by isp-1 mutation from 43% to 26% (p<0.001) and did not significantly affect wild-type longevity. WT subjected to control RNAi: N = 90, m = 18.1 days; WT subjected to cdr-2 RNAi: N = 87, m = 19.1 days; isp-1(−) mutants subjected to control RNAi: N = 89, m = 22.4 days; isp-1 (−) mutants subjected to cdr-2 RNAi: N = 89, m = 20.1 days. In a second trial, cdr-2 RNAi decreased the lifespan extension produced by isp-1 mutation from 24% to 11% (p<0.001) (Table S4). Lifespans were determined at 20°C. D) fstr-1/2 RNAi did not shorten the lifespan of isp-1 mutants. isp-1(−) mutants subjected to control RNAi: N = 108, m = 24.6 days; isp-1 (−) mutants subjected to fstr-1/2 RNAi: N = 104, m = 23.6 days. These experiments were repeated twice more with similar results (Table S4).
Figure 3 Lifespan measurements of long-lived mitochondrial mutants subjected to RNAi of individual retrograde-response genes. A) aqp-1 RNAi significantly decreased the lifespan extension produced by clk-1 mutations from 26% (control) to 7%; p<0.05 (left panel) and from 17% (control) to 0%; p<0.0001 (right panel). Left panel - WT subjected to control (vector-only) RNAi: N = 103, m = 13.4 days; clk-1(−) mutants subjected to control RNAi: N = 105, m = 16.9 days; clk-1(−) mutants subjected to aqp-1 RNAi: N = 105, m = 14.4 days. Right panel - WT subjected to control (vector-only) RNAi: N = 77, m = 15.1 days; clk-1(−) mutants subjected to control RNAi: N = 137, m = 17.3 days; clk-1(−) mutants subjected to aqp-1 RNAi: N = 70, m = 15.1 days. aqp-1 RNAi did not significantly affect WT lifespan (Figure S1). B) fstr-1/2 RNAi significantly decreased the lifespan extension produced by clk-1 mutation from 26% to 3%, p<0.01 (left panel) and from 17% (control) to 0%; p<0.0001 (right panel). Left panel - WT subjected to control RNAi, same as in Figure 2A; clk-1(−) mutants subjected to control RNAi, same as in Figure 2A; clk-1(−) mutants subjected to fstr-1/2 RNAi: N = 108, m = 13.8 days. Right Panel - WT subjected to control (vector-only) RNAi: N = 77, m = 15.1 days; clk-1(−) mutants subjected to control RNAi: N = 137, m = 17.3 days; clk-1(−) mutants subjected to fstr-1/2 RNAi: N = 63, m = 14.5 days. fstr-1/2 RNAi did not significantly affect WT lifespan (Figure S1). C) cdr-2 RNAi suppressed the longevity increase produced by isp-1 mutation from 43% to 26% (p<0.001) and did not significantly affect wild-type longevity. WT subjected to control RNAi: N = 90, m = 18.1 days; WT subjected to cdr-2 RNAi: N = 87, m = 19.1 days; isp-1(−) mutants subjected to control RNAi: N = 89, m = 22.4 days; isp-1 (−) mutants subjected to cdr-2 RNAi: N = 89, m = 20.1 days. In a second trial, cdr-2 RNAi decreased the lifespan extension produced by isp-1 mutation from 24% to 11% (p<0.001) (Table S4). Lifespans were determined at 20°C. D) fstr-1/2 RNAi did not shorten the lifespan of isp-1 mutants. isp-1(−) mutants subjected to control RNAi: N = 108, m = 24.6 days; isp-1 (−) mutants subjected to fstr-1/2 RNAi: N = 104, m = 23.6 days. These experiments were repeated twice more with similar results (Table S4).CC BY · PubMed Central
Figure 4 fstr-1/2 RNAi speeds up clk-1(−) animals. A) Time to adulthood. clk-1 mutants take much longer to reach adulthood than wild-type animals. This rate of development is accelerated by fstr-1/2 RNAi. In contrast, fstr-1/2 RNAi slowed the growth rate of wild type. These effects were very robust and were observed in every experiment. WT subjected to control RNAi: 47.4±1.6 hours; WT subjected to fstr-1/2 RNAi: 53.2±1.7 hours; clk-1(−) mutants subjected to control RNAi: 82.2±1.2 hours; clk-1(−) mutants subjected to fstr-1/2 RNAi: 72±1.7 hours. B) Boxplots illustrating thrashing rates measured on day 3 of adulthood. fstr-1/2 RNAi treatment significantly reduced the average thrashing rate of wild-type animals and significantly increased the average thrashing rate of clk-1(−) mutants. WT subjected to control RNAi: 115.6±3.1 thrashes/min; WT subjected to fstr-1/2 RNAi: 97.5±4.3 thrashes/min; clk-1(−) mutants subjected to control RNAi: 61.2±5 thrashes/min; clk-1(−) mutants subjected to fstr-1/2 RNAi: 78.9±5.7 thrashes/min. C) Boxplots illustrating pumping rates. fstr-1/2 RNAi decreased the average pumping rate of wild type and increased the pumping rate of clk-1(−) mutants. WT subjected to control RNAi: 273.3±41.1 pumps/min; WT subjected to fstr-1/2 RNAi: 231.8±24.7 pumps/min; clk-1(−) mutants subjected to control RNAi: 188.5±41 pumps/min; clk-1(−) mutants subjected to fstr-1/2 RNAi: 238.9±36.4 pumps/min. In Figs. 3A, 3B and 3C, error bars depict SEM; * depicts a significance of p<0.05 when compared to controls, ** depicts a significance of p<0.008 when compared to controls, ¥¥ depicts a significance of p<0.008. P<0.008 is the cut-off set by the Bonferroni correction for multiple comparisons. D) HPLC analysis of quinone content. The chromatograms show a representative run of three independent experiments for each of the different conditions (WT subjected to control RNAi, WT subjected to fstr-1/2 RNAi, clk-1(−) mutants subjected to control RNAi and clk-1(−) mutants subjected to fstr-1/2 RNAi). The Q9 peak is absent from clk-1(−) animals and instead the intermediate DMQ9 peak is present. fstr-1/2 RNAi had no effect on Q9 levels in wild-type or clk-1(−) mutants, in clk-1 mutants Q9 levels remained below the detection threshold.
Figure 4 fstr-1/2 RNAi speeds up clk-1(−) animals. A) Time to adulthood. clk-1 mutants take much longer to reach adulthood than wild-type animals. This rate of development is accelerated by fstr-1/2 RNAi. In contrast, fstr-1/2 RNAi slowed the growth rate of wild type. These effects were very robust and were observed in every experiment. WT subjected to control RNAi: 47.4±1.6 hours; WT subjected to fstr-1/2 RNAi: 53.2±1.7 hours; clk-1(−) mutants subjected to control RNAi: 82.2±1.2 hours; clk-1(−) mutants subjected to fstr-1/2 RNAi: 72±1.7 hours. B) Boxplots illustrating thrashing rates measured on day 3 of adulthood. fstr-1/2 RNAi treatment significantly reduced the average thrashing rate of wild-type animals and significantly increased the average thrashing rate of clk-1(−) mutants. WT subjected to control RNAi: 115.6±3.1 thrashes/min; WT subjected to fstr-1/2 RNAi: 97.5±4.3 thrashes/min; clk-1(−) mutants subjected to control RNAi: 61.2±5 thrashes/min; clk-1(−) mutants subjected to fstr-1/2 RNAi: 78.9±5.7 thrashes/min. C) Boxplots illustrating pumping rates. fstr-1/2 RNAi decreased the average pumping rate of wild type and increased the pumping rate of clk-1(−) mutants. WT subjected to control RNAi: 273.3±41.1 pumps/min; WT subjected to fstr-1/2 RNAi: 231.8±24.7 pumps/min; clk-1(−) mutants subjected to control RNAi: 188.5±41 pumps/min; clk-1(−) mutants subjected to fstr-1/2 RNAi: 238.9±36.4 pumps/min. In Figs. 3A, 3B and 3C, error bars depict SEM; * depicts a significance of p<0.05 when compared to controls, ** depicts a significance of p<0.008 when compared to controls, ¥¥ depicts a significance of p<0.008. P<0.008 is the cut-off set by the Bonferroni correction for multiple comparisons. D) HPLC analysis of quinone content. The chromatograms show a representative run of three independent experiments for each of the different conditions (WT subjected to control RNAi, WT subjected to fstr-1/2 RNAi, clk-1(−) mutants subjected to control RNAi and clk-1(−) mutants subjected to fstr-1/2 RNAi). The Q9 peak is absent from clk-1(−) animals and instead the intermediate DMQ9 peak is present. fstr-1/2 RNAi had no effect on Q9 levels in wild-type or clk-1(−) mutants, in clk-1 mutants Q9 levels remained below the detection threshold.CC BY · PubMed Central
Figure 5 fstr-1/2 RNAi inhibits expression of clk-1 retrograde-response genes. The graph shows the effect of fstr-1/2 RNAi on the degree of up-regulation of the five individual clk-1 retrograde-response genes we examined, as determined by quantitative RT-PCR. (**) represents a significance of p<0.01, (*) represents a significance of p<0.05, in comparing mRNA levels from clk-1(−); fstr-1/2(RNAi) animals vs. clk-1(−) control animals. Each bar represents the average of 3 independent biological repeats. Error bars are ±SEM. clk-1(−) animals subjected to control RNAi showed significantly higher expression than did wild type subjected to control RNAi (p<0.05) for all genes tested. With the exception of gpd-2, all genes showed a significant decrease in expression (p<0.05) in the presence of fstr-1/2 RNAi. Note that gpd-2 shared the trend, with p = 0.061, and was clearly affected when assayed using the pgpd-2::gfp reporter in vivo (Figure 7 and Figure S5).
Figure 5 fstr-1/2 RNAi inhibits expression of clk-1 retrograde-response genes. The graph shows the effect of fstr-1/2 RNAi on the degree of up-regulation of the five individual clk-1 retrograde-response genes we examined, as determined by quantitative RT-PCR. (**) represents a significance of p<0.01, (*) represents a significance of p<0.05, in comparing mRNA levels from clk-1(−); fstr-1/2(RNAi) animals vs. clk-1(−) control animals. Each bar represents the average of 3 independent biological repeats. Error bars are ±SEM. clk-1(−) animals subjected to control RNAi showed significantly higher expression than did wild type subjected to control RNAi (p<0.05) for all genes tested. With the exception of gpd-2, all genes showed a significant decrease in expression (p<0.05) in the presence of fstr-1/2 RNAi. Note that gpd-2 shared the trend, with p = 0.061, and was clearly affected when assayed using the pgpd-2::gfp reporter in vivo (Figure 7 and Figure S5).CC BY · PubMed Central
Figure 6 fstr-1 is expressed in the intestine and three neurons. The figure shows the expression of a pfstr-1::mCherry promoter fusion in clk-1(−) mutants. The transgene is expressed in the intestine, especially in anterior cells, as well as in RIH and I1L/R neurons. Small arrows point to cell bodies of I1L/R neurons, with their characteristic processes visible; large arrows point to the cell body of the RIH neuron. The small panel shows a more detailed view of RIH neuron. Scale bar represents 20 µm. We observed a similar, but fainter, mCherry distribution in a wild-type background (not shown).
Figure 6 fstr-1 is expressed in the intestine and three neurons. The figure shows the expression of a pfstr-1::mCherry promoter fusion in clk-1(−) mutants. The transgene is expressed in the intestine, especially in anterior cells, as well as in RIH and I1L/R neurons. Small arrows point to cell bodies of I1L/R neurons, with their characteristic processes visible; large arrows point to the cell body of the RIH neuron. The small panel shows a more detailed view of RIH neuron. Scale bar represents 20 µm. We observed a similar, but fainter, mCherry distribution in a wild-type background (not shown).CC BY · PubMed Central
Figure 7 fstr-1/2 RNAi does not affect gpd-2 expression in an isp-1 mutant. Worms harboring a pgpd-2::gfp promoter fusion were ranked as: Dim Fluorescence, Medium Fluorescence and High Fluorescence based on visual inspection. Each bar represents a different population (N = 80 worms). Two separate observations were made for each condition. See Figure S5 for representative high- and dim-fluorescence populations.
Figure 7 fstr-1/2 RNAi does not affect gpd-2 expression in an isp-1 mutant. Worms harboring a pgpd-2::gfp promoter fusion were ranked as: Dim Fluorescence, Medium Fluorescence and High Fluorescence based on visual inspection. Each bar represents a different population (N = 80 worms). Two separate observations were made for each condition. See Figure S5 for representative high- and dim-fluorescence populations.CC BY · PubMed Central
Figure 8 C. elegans retrograde response. The picture diagrams metabolic changes thought to occur during the yeast retrograde response (Butow and Avadhani 2004). “++” indicates that these same changes are observed in the C. elegans retrograde response. Impairment of electron flow during oxidative phosphorylation is predicted to have two effects. The first is an increase in ROS, due to increased likelihood of electrons transferring to free oxygen (Lenaz 2001). Consistent with increased ROS stress (which we did not assay directly), we observed an increase in cell-protective genes. Secondly, the Krebs cycle is disrupted because the enzyme succinate dehydrogenase is an integral part of both the electron transport chain and of the Krebs cycle. When succinate dehydrogenase oxidizes succinate into fumarate, it feeds electrons into the ETC, and when this flow is blocked, the enzyme's activity is inhibited. The Krebs cycle is necessary for synthesis of glutamate, which in turn is required for amino acid metabolism. Impairment of the electron transport chain leads to decreased glutamate production. Possibly in order to counteract this decrease in glutamate production, the cell induces anaplerotic pathways that feed intermediates into the Krebs cycle, thus allowing production of glutamate. Under conditions of impaired respiration, glycolytic gene expression increases, consistent with glycolysis' becoming a major source of ATP. Consistent with a compensatory response, expression of genes involved in oxidative phosphorylation is up-regulated. OAA, Oxaloacetate; GLU, glutamate; ETC, electron transport chain; α-KG, α-ketoglutarate.
Figure 8 C. elegans retrograde response. The picture diagrams metabolic changes thought to occur during the yeast retrograde response (Butow and Avadhani 2004). “++” indicates that these same changes are observed in the C. elegans retrograde response. Impairment of electron flow during oxidative phosphorylation is predicted to have two effects. The first is an increase in ROS, due to increased likelihood of electrons transferring to free oxygen (Lenaz 2001). Consistent with increased ROS stress (which we did not assay directly), we observed an increase in cell-protective genes. Secondly, the Krebs cycle is disrupted because the enzyme succinate dehydrogenase is an integral part of both the electron transport chain and of the Krebs cycle. When succinate dehydrogenase oxidizes succinate into fumarate, it feeds electrons into the ETC, and when this flow is blocked, the enzyme's activity is inhibited. The Krebs cycle is necessary for synthesis of glutamate, which in turn is required for amino acid metabolism. Impairment of the electron transport chain leads to decreased glutamate production. Possibly in order to counteract this decrease in glutamate production, the cell induces anaplerotic pathways that feed intermediates into the Krebs cycle, thus allowing production of glutamate. Under conditions of impaired respiration, glycolytic gene expression increases, consistent with glycolysis' becoming a major source of ATP. Consistent with a compensatory response, expression of genes involved in oxidative phosphorylation is up-regulated. OAA, Oxaloacetate; GLU, glutamate; ETC, electron transport chain; α-KG, α-ketoglutarate.CC BY · PubMed Central
Figure 9 C. elegans mitochondrial mutants activate similar transcriptional responses in different ways. In this model, clk-1 mutation decreases ubiquinone levels, which increases fstr-1 expression (possibly with the assistance of fstr-2, which is expressed constitutively). fstr-1/2 are then necessary for expression of other genes that are part of the retrograde response, which in turn are likely to be responsible for the longevity and slowed phenotypes. clk-1, isp-1 and cyc-1(RNAi) mutants show similar transcriptional responses, however, fstr-1/2 is necessary for the transcriptional response of clk-1 but not isp-1 mutants.
Figure 9 C. elegans mitochondrial mutants activate similar transcriptional responses in different ways. In this model, clk-1 mutation decreases ubiquinone levels, which increases fstr-1 expression (possibly with the assistance of fstr-2, which is expressed constitutively). fstr-1/2 are then necessary for expression of other genes that are part of the retrograde response, which in turn are likely to be responsible for the longevity and slowed phenotypes. clk-1, isp-1 and cyc-1(RNAi) mutants show similar transcriptional responses, however, fstr-1/2 is necessary for the transcriptional response of clk-1 but not isp-1 mutants.CC BY · PubMed Central

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Metadata

Authors
Cristina, D., Cary, M., Lunceford, A., Clarke, C., & Kenyon, C.
Affiliations
  • University of California, San Francisco (US)
  • University of California, Los Angeles (US)
Corresponding author
Kenyon, Cynthia
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2009-04-10
Volume
5
Issue
4
Pages
e1000450
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1000450
PMC
PMC2660839
OpenAlex
W2086324577
Cited by
166
References
41
Citations by year
2026: 8 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 10 · 2021: 6 · 2020: 15 · 2019: 10 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 21 · 2013: 5 · 2012: 12
FWCI
4.71
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
Funders
  • Genome Canada
  • Genome British Columbia
  • National Institutes of Health
  • University of California, San Francisco
  • National Center for Research Resources
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
mitochondrial respiration inhibition, coenzyme Q10, clk-1, retrograde response, lifespan extension, aging, Caenorhabditis elegans, mitochondrial mutants, gene expression response
MeSH terms
Animals, Behavior, Animal, Gene Expression Regulation, Longevity, Mitochondria, Mutation, Caenorhabditis elegans, Cell Respiration, Models, Animal, Caenorhabditis elegans Proteins

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