Figure 5. Working model: CARS‐CaMKK2‐AMPKγ2 pathway activates AMPK to promote cell survival under cystine starvation condition.

In the presence of cyst(e)ine, cysteine blocked the interaction of CARS with AMPKγ2, the AMPK complex is in an inactive state. In the deficiency of cystine, CARS is able to bind to AMPKγ2, thus recruiting CaMKK2 to the AMPK complex and leading to phosphorylation and activation of AMPK, which ultimately promotes cell survival.