Over-expression of the constitutive AMPylase FIC-1(E274G) does not deplete cellular ATP pools in C. elegans

Protein AMPylation has emerged as a posttranslational protein modification regulating cellular proteostasis. AMPylation is conferred by Fic AMPylases, which catalyze the covalent attachment of AMP to target proteins at the expense of ATP. Over-expression of constitutive-active Fic AMPylases is toxic. Here, we test the hypothesis that excessive Fic AMPylase activity could deplete cellular ATP pools, leading to cell death. We find that increased/decreased Fic AMPylase activity only alters cellular ATP concentrations by approximately 15%. This suggests that hyper-AMPylation-mediated cell death is likely not the consequence of cellular ATP depletion.