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An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans

Sider Penkov, Bharath Kumar Raghuraman, Cihan Erkut, Jana Oertel, Roberta Galli, Eduardo Jacobo Miranda Ackerman, Daniela Vorkel, Jean-Marc Verbavatz, Edmund Koch, Karim Fahmy, Andrej Shevchenko, Teymuras V. Kurzchalia
doi: https://doi.org/10.1101/323956
Sider Penkov
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
2Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany
3Institute for Clinical Chemistry and Laboratory Medicine, University Clinic and Medical Faculty, TU Dresden, Dresden, Germany
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  • For correspondence: kurzchalia@mpi-cbg.de sider.penkov1@tu-dresden.de
Bharath Kumar Raghuraman
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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Cihan Erkut
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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Jana Oertel
4Institute of Resource Ecology at the Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
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Roberta Galli
5Faculty of Medicine Carl Gustav Carus, Department of Anesthesiology and Intensive Care Medicine, Clinical Sensoring and Monitoring, TU Dresden, Dresden, Germany
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Eduardo Jacobo Miranda Ackerman
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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Daniela Vorkel
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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Jean-Marc Verbavatz
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
6Institut Jacques Monod, Université Paris Diderot, Paris, France
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Edmund Koch
5Faculty of Medicine Carl Gustav Carus, Department of Anesthesiology and Intensive Care Medicine, Clinical Sensoring and Monitoring, TU Dresden, Dresden, Germany
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Karim Fahmy
4Institute of Resource Ecology at the Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
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Andrej Shevchenko
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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Teymuras V. Kurzchalia
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
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  • For correspondence: kurzchalia@mpi-cbg.de sider.penkov1@tu-dresden.de
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Abstract

The balance between growth and quiescence depends on the global metabolic state. The dauer larva of C. elegans, a developmentally arrested stage for survival under adverse environment, undergoes a major metabolic transition. Here, we show that this switch involves the concerted activity of several regulatory pathways. Whereas the steroid hormone receptor DAF-12 controls dauer morphogenesis, the insulin pathway maintains low energy expenditure through DAF-16/FoxO, which also requires AAK-2/AMPKα. DAF-12 and AAK-2 separately promote a shift in the molar ratios between competing enzymes at two key branch points within the central carbon metabolic pathway. This way, carbon atoms are diverted from the TCA cycle and directed to gluconeogenesis. When both AAK-2 and DAF-12 are suppressed, the TCA cycle is active and the developmental arrest is bypassed. Hence, the metabolic status of each developmental stage is defined by stoichiometric ratios within the constellation of metabolic enzymes and controls the transition between growth and quiescence.

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Posted December 27, 2019.
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An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans
Sider Penkov, Bharath Kumar Raghuraman, Cihan Erkut, Jana Oertel, Roberta Galli, Eduardo Jacobo Miranda Ackerman, Daniela Vorkel, Jean-Marc Verbavatz, Edmund Koch, Karim Fahmy, Andrej Shevchenko, Teymuras V. Kurzchalia
bioRxiv 323956; doi: https://doi.org/10.1101/323956
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An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans
Sider Penkov, Bharath Kumar Raghuraman, Cihan Erkut, Jana Oertel, Roberta Galli, Eduardo Jacobo Miranda Ackerman, Daniela Vorkel, Jean-Marc Verbavatz, Edmund Koch, Karim Fahmy, Andrej Shevchenko, Teymuras V. Kurzchalia
bioRxiv 323956; doi: https://doi.org/10.1101/323956

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