An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans

Edited by Gregory A. Petsko, Brandeis University, Waltham, MA, and approved January 19, 2007
March 27, 2007
104 (13) 5489-5494

Abstract

Protection of poikilothermic animals from seasonal cold is widely regarded as being causally linked to changes in the unsaturation of membrane phospholipids, yet in animals this proposition remains formally untested. We have now achieved this by the genetic manipulation of lipid biosynthesis of Caenorhabditis elegans independent of temperature. Worms transferred from 25°C to 10°C develop over several days a much-increased tolerance of lethal cold (0°C) and also an increased phospholipid unsaturation, as in higher animal models. Of the three C. elegans Δ9-desaturases, transcript levels of fat-7 only were up-regulated by cold transfer. RNAi suppression of fat-7 caused the induction of fat-5 desaturase, so to control desaturase expression we combined RNAi of fat-7 with a fat-5 knockout. These fat-5/fat-7 manipulated worms displayed the expected negative linear relationship between lipid saturation and cold tolerance at 0°C, an outcome confirmed by dietary rescue. However, this change in lipid saturation explains just 16% of the observed difference between cold tolerance of animals held at 25°C and 10°C. Thus, although the manipulated lipid saturation affects the tolerable thermal window, and altered Δ9-desaturase expression accounts for cold-induced lipid adjustments, the effect is relatively small and none of the lipid manipulations were sufficient to convert worms between fully cold-sensitive and fully cold-tolerant states. Critically, transfer of 10°C-acclimated worms back to 25°C led to them restoring the usual cold-sensitive phenotype within 24 h despite retaining a lipid profile characteristic of 10°C worms. Other nonlipid mechanisms of acquired cold protection clearly dominate inducible cold tolerance.

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Acknowledgments

We thank Dr. D. Tocher, J. Dick, and M. Prescott for help with mass spectrometry; Drs. J. Watts, G. Lithgow, and A. Postle for helpful discussions; Dr. S. Mitani for cultures of the fat-5 mutant strain; and anonymous reviewers for insightful comments. This work was supported by a grant from Biotechnology and Biological Sciences Research Council (U.K.). P.M. is a Royal Society Dorothy Hodgkin Fellow (U.K.).

Supporting Information

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 104 | No. 13
March 27, 2007
PubMed: 17369360

Classifications

Submission history

Received: November 2, 2006
Published online: March 27, 2007
Published in issue: March 27, 2007

Keywords

  1. Δ9-acyl desaturase
  2. lipid composition
  3. RNAi

Acknowledgments

We thank Dr. D. Tocher, J. Dick, and M. Prescott for help with mass spectrometry; Drs. J. Watts, G. Lithgow, and A. Postle for helpful discussions; Dr. S. Mitani for cultures of the fat-5 mutant strain; and anonymous reviewers for insightful comments. This work was supported by a grant from Biotechnology and Biological Sciences Research Council (U.K.). P.M. is a Royal Society Dorothy Hodgkin Fellow (U.K.).

Notes

This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0609590104/DC1.

Authors

Affiliations

Patricia Murray
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom
Scott A. L. Hayward
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom
Gregor G. Govan
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom
Andrew Y. Gracey
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom
*Present address: Marine Environmental Biology, University of Southern California, Los Angeles, CA 90089.
Andrew R. Cossins [email protected]
School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, United Kingdom

Notes

To whom correspondence should be addressed. E-mail: [email protected]
Author contributions: P.M. and S.A.L.H. contributed equally to this work; P.M., S.A.L.H., A.Y.G., and A.R.C. designed research; P.M., S.A.L.H., and G.G.G. performed research; A.Y.G. contributed new reagents/analytic tools; P.M., S.A.L.H., and A.R.C. analyzed data; and P.M., S.A.L.H., and A.R.C. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans
    Proceedings of the National Academy of Sciences
    • Vol. 104
    • No. 13
    • pp. 5253-5704

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