Allosteric regulation of C. elegans AMP-activated protein kinase

AMP-activated protein kinase (AMPK) is a key metabolic regulator which responds to changes in the AMP:ATP ratio within cells. In response to high AMP levels, AMPK promotes a metabolic shift towards increased catabolism and autophagy to restore cellular energy and maintain homeostasis. In C. elegans, AMPK is important for controlling a multitude of functions including metabolism, reproductive health, and lifespan. AMPK is a heterotrimeric protein consisting of α catalytic, β linker, and γ regulatory subunits. Active AMPK is characterised by phosphorylation of the α subunit. It is also regulated allosterically by the nucleotide AMP binding within the γ subunit. C. elegans have five different AMPKγ subunits and their primary amino acid sequence implies two different modes of AMP-binding. Modifying the ability of AMPKγ to bind adenine nucleotides could directly impact how effectively AMPK manages energy homeostasis. Despite the importance of the γ subunit, most C. elegans AMPK research has focused on the catalytic α subunit. Here, we genetically dissect the functional role of the different γ subunits in relation to physiology and lifespan. We show that in normal animals, three of these γ subunits ( aakg-1, aakg-2, and aakg-3 ) are required for normal responses to AMP, and contribute to normal fecundity and lifespan.