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Science 334 (6057): 802-805

Copyright © 2011 by the American Association for the Advancement of Science

Influence of Inositol Pyrophosphates on Cellular Energy Dynamics

Zsolt Szijgyarto,1 Assegid Garedew,2 Cristina Azevedo,1 Adolfo Saiardi1,*

Abstract: With its high-energy phosphate bonds, adenosine triphosphate (ATP) is the main intracellular energy carrier. It also functions in most signaling pathways, as a phosphate donor or a precursor for cyclic adenosine monophosphate. We show here that inositol pyrophosphates participate in the control of intracellular ATP concentration. Yeasts devoid of inositol pyrophosphates have dysfunctional mitochondria but, paradoxically, contain four times as much ATP because of increased glycolysis. We demonstrate that inositol pyrophosphates control the activity of the major glycolytic transcription factor GCR1. Thus, inositol pyrophosphates regulate ATP concentration by altering the glycolytic/mitochondrial metabolic ratio. Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems.

1 Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, and Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
2 The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.

* To whom correspondence should be addressed. E-mail: dmcbado{at}ucl.ac.uk

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