Champion Margaret, Truttmann Matthias C
University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI.
MicroPubl Biol. 2021 Jun 25;2021. doi: 10.17912/micropub.biology.000409.
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.
蛋白质腺苷酸化已成为一种调节细胞蛋白质稳态的翻译后蛋白质修饰。腺苷酸化由Fic腺苷酸酶介导，该酶催化将AMP以ATP为代价共价连接到靶蛋白上。组成型活性Fic腺苷酸酶的过表达具有毒性。在这里，我们检验了这样一个假设，即过量的Fic腺苷酸酶活性可能会耗尽细胞内的ATP池，导致细胞死亡。我们发现Fic腺苷酸酶活性的增加/降低仅使细胞ATP浓度改变约15%。这表明高腺苷酸化介导的细胞死亡可能不是细胞ATP耗竭的结果。
