CARS senses cysteine deprivation to activate AMPK for cell survival

ABSTRACT: Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is an important cellular metabolite-sensing enzyme that can directly sense not only changes in ATP but also in metabolites associated with carbohydrates and fatty acids. However, less is known about whether and how AMPK senses variations in cellular amino acids. Here, we show that cysteine deficiency significantly triggers Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)-mediated activation of AMPK. In addition, we found that CaMKK2 directly associates with cysteinyl-tRNA synthetase (CARS), which then binds to AMPK?2 under cysteine deficiency to activate AMPK. Interestingly, we discovered that cysteine inhibits the binding of CARS to AMPK?2, and thus, under cysteine-deficiency conditions wherein the inhibitory ef

SUBMITTER: Mengqiu Yuan 

PROVIDER: S-SCDT-EMBOJ-2021-108028 | biostudies-other |

REPOSITORIES: biostudies-other