AMPK: Sensing Glucose as well as Cellular Energy Status

Publication date: Available online 16 November 2017
Source:Cell Metabolism
Author(s): Sheng-Cai Lin, D. Grahame Hardie
Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation. This nutrient-sensing mechanism activates AMPK but also primes it for further activation if cellular energy status subsequently falls. Glucose sensing at the lysosome, in which AMPK and other components of the activation complex act antagonistically with another key nutrient sensor, mTORC1, may have been one of the ancestral roles of AMPK.

Teaser

Recent findings show that AMPK, usually thought of as an energy sensor activated by changes in adenine nucleotides during metabolic stress, can also sense low availability of glucose via a novel, AMP-independent mechanism. Lin and Hardie review these latest developments and place them into context with the canonical energy-sensing mechanism.


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