TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants

Maruf H. Khan, Melissa Ligon, Lauren R. Hussey, Bryce Hufnal, Robert Farber, Erin Munkácsy, Amanda Rodriguez, Andy Dillow, Erynn Kahlig, Shane L. Rea

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors - AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)- interacting protein TAF-4 - were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF- 1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.

Original languageEnglish (US)
Pages (from-to)741-758
Number of pages18
JournalAging
Volume5
Issue number10
StatePublished - Oct 2013

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Life Expectancy
Transcription Factors
Wild Animals
Oxidative Phosphorylation
Caenorhabditis elegans
Electron Transport
RNA Interference
Fertility
Phenotype
Proteins

Keywords

  • Aha-1
  • C.elegans
  • Ceh-18
  • Clk-1
  • Hif-1
  • Isp-1
  • Jun-1
  • Lifespan
  • Mit mutants
  • Mitochondria
  • Nhr-27
  • Nhr-49
  • Taf-4

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Khan, M. H., Ligon, M., Hussey, L. R., Hufnal, B., Farber, R., Munkácsy, E., ... Rea, S. L. (2013). TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging, 5(10), 741-758.

TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. / Khan, Maruf H.; Ligon, Melissa; Hussey, Lauren R.; Hufnal, Bryce; Farber, Robert; Munkácsy, Erin; Rodriguez, Amanda; Dillow, Andy; Kahlig, Erynn; Rea, Shane L.

In: Aging, Vol. 5, No. 10, 10.2013, p. 741-758.

Research output: Contribution to journalArticle

Khan, MH, Ligon, M, Hussey, LR, Hufnal, B, Farber, R, Munkácsy, E, Rodriguez, A, Dillow, A, Kahlig, E & Rea, SL 2013, 'TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants', Aging, vol. 5, no. 10, pp. 741-758.
Khan MH, Ligon M, Hussey LR, Hufnal B, Farber R, Munkácsy E et al. TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging. 2013 Oct;5(10):741-758.
Khan, Maruf H. ; Ligon, Melissa ; Hussey, Lauren R. ; Hufnal, Bryce ; Farber, Robert ; Munkácsy, Erin ; Rodriguez, Amanda ; Dillow, Andy ; Kahlig, Erynn ; Rea, Shane L. / TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. In: Aging. 2013 ; Vol. 5, No. 10. pp. 741-758.
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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 identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors - AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)- interacting protein TAF-4 - were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF- 1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.",
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AU - Khan, Maruf H.

AU - Ligon, Melissa

AU - Hussey, Lauren R.

AU - Hufnal, Bryce

AU - Farber, Robert

AU - Munkácsy, Erin

AU - Rodriguez, Amanda

AU - Dillow, Andy

AU - Kahlig, Erynn

AU - Rea, Shane L.

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N2 - 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 identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors - AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)- interacting protein TAF-4 - were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF- 1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.

AB - 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 identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors - AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)- interacting protein TAF-4 - were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF- 1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.

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