Involvement of aak-2 and insulin-like signalling mutations in the cellular stress response as determined by an in vivo ATP sensor C. elegans strain

The AMP-activated protein kinase (AMPK) plays a key role in the regulation of critical ratios of ATP:ADP and ATP:AMP. AMPK is activated by any stress treatment that interferes with ATP levels. C.elegans aak-2 mutants that do not have an active AMP activated protein kinase, were found to be more sensitive than wild type worms to killing by either starvation, high temperature or mitochondrial poisoning (1). Insulin-like signalling mutants also have altered sensitivity to stress. With regards to aging networks, it has recently been shown that lifespan extension caused by daf-2\/insulin-like signalling mutations is highly dependent on aak-2, and that aak-2 and daf-16 function in parallel responding to overlapping but different inputs (2). We are interested in the stress response aspect of this interrelationship and have exposed aak-2 and insulin-like signalling mutants to various stresses. We have chosen stresses known to result in changes in the AMP:ATP ratio such as heat and inhibitors of mitochondrial respiration and stresses such as hyperosmolarity which have unknown effects. We transferred a transgenic firefly luciferase gene to aak-2 (ok524), daf-2 (e1370) and daf-16 (mu86) mutant strains to enable a rapid real time indication of ATP levels in C.elegans following the exposure to the above stresses (3, see also Lagido et al. accompanying abstract). In addition we determined viability after 24h stress exposure by probing of the worms with a needle. We will discuss the interrelationship of aak-2 and insulin-like signalling in the context of the stress response. (1) Apfeld J. et al. Genes & Development (2004) 18: 3004-3009. (2) Curtis R. et al. Aging Cell (2006) 5, 119-126. (3) Lagido C. et al. FEMS Lett. (2001) 36-39.