PerspectiveCell Biology

Pyro-Technic Control of Metabolism

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Science  11 Nov 2011:
Vol. 334, Issue 6057, pp. 770-771
DOI: 10.1126/science.1214727

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A report by Szijgyarto et al. on page 802 of this issue (1) reports some striking evidence for a previously unknown system of intracellular metabolic sensing in eukaryotic cells involving inositol pyrophosphates and reveals some fascinating molecular details of how it may work. The key molecule involved in this potential homeostatic mechanism is an inositol pyrophosphate, inositol 1,2,3,4,6-pentaphosphate 5-pyrophosphate, or IP7. IP7 is formed by phosphorylation (strictly, pyrophosphorylation) of the ubiquitous inositol phosphate, IP6, on the 5-phosphate moiety by a family of kinases, the IP6 5-kinases (encoded by three genes in mammals; the budding yeast gene is Kcs1) (2). It is further pyrophosphorylated in the 1-position to form IP8 by another family of kinases, the Vip1 family (3, 4), but the evidence of Szijgyarto et al. suggests that IP7 is the key molecule in controlling cellular energeitcs.