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Penkov, S. ; Raghuraman, B.K.* ; Erkut, C.* ; Oertel, J.* ; Galli, R.* ; Ackerman, E.J.M.* ; Vorkel, D.* ; Verbavatz, J.M.* ; Koch, E.* ; Fahmy, K.* ; Shevchenko, A.* ; Kurzchalia, T.V.*

A metabolic switch regulates the transition between growth and diapause in C. elegans.

BMC Biol. 18:31 (2020)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Background Metabolic activity alternates between high and low states during different stages of an organism's life cycle. During the transition from growth to quiescence, a major metabolic shift often occurs from oxidative phosphorylation to glycolysis and gluconeogenesis. We use the entry of Caenorhabditis elegans into the dauer larval stage, a developmentally arrested stage formed in response to harsh environmental conditions, as a model to study the global metabolic changes and underlying molecular mechanisms associated with growth to quiescence transition. Results Here, we show that the metabolic 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/AMPK alpha. 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 diverting carbon atoms from the TCA cycle and directing them to gluconeogenesis. When both AAK-2 and DAF-12 are suppressed, the TCA cycle is active and the developmental arrest is bypassed. Conclusions The metabolic status of each developmental stage is defined by stoichiometric ratios within the constellation of metabolic enzymes driving metabolic flux and controls the transition between growth and quiescence.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Caenorhabditis-elegans; Life-span; Stereoselective-synthesis; Dietary Restriction; Developmental Age; Energy-metabolism; Anaerobic Shift; Dauer Formation; Long; Longevity
e-ISSN 1741-7007
Journal BMC Biology
Quellenangaben Volume: 18, Issue: 1, Pages: , Article Number: 31 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)