2013
DOI: 10.18632/aging.100604
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Abstract: While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and … Show more

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Cited by 44 publications
(55 citation statements)
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References 42 publications
(67 reference statements)
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“…Like other α‐ketoglutarate‐dependent hydroxylases, EGL‐9 consumes α‐ketoglutarate during its catalytic cycle (Dowell & Hadley, 1992). Surprisingly, HIF‐1 is constitutively active under normoxic conditions in Mit mutants (Lee et al ., 2010; Khan et al ., 2013), suggesting EGL‐9 could be a target of 3M2OB, 3M2OV, 4M2OV, and/or pyruvate in these animals. We tested whether supplementation of these four α‐ketoacids could stabilize a functional HIF‐1:: myc translational reporter when provided to 1‐day‐old adult worms.…”
Section: Resultsmentioning
confidence: 97%
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“…Like other α‐ketoglutarate‐dependent hydroxylases, EGL‐9 consumes α‐ketoglutarate during its catalytic cycle (Dowell & Hadley, 1992). Surprisingly, HIF‐1 is constitutively active under normoxic conditions in Mit mutants (Lee et al ., 2010; Khan et al ., 2013), suggesting EGL‐9 could be a target of 3M2OB, 3M2OV, 4M2OV, and/or pyruvate in these animals. We tested whether supplementation of these four α‐ketoacids could stabilize a functional HIF‐1:: myc translational reporter when provided to 1‐day‐old adult worms.…”
Section: Resultsmentioning
confidence: 97%
“…These data illustrate that at least one compound, pyruvate, that accumulates in the exometabolome of Mit mutants and is sufficient to increase the lifespan of wild‐type worms (Fig. 2B, lower panel, black lines), is also sufficient to stabilize a factor known to be essential for Mit mutant longevity, namely HIF‐1 (Lee et al ., 2010; Khan et al ., 2013). Indeed, the pro‐longevity effect of pyruvate on wild‐type worms is abrogated following disruption of hif‐1 (Fig.…”
Section: Resultsmentioning
confidence: 99%
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