P09 : Regulation of mTOR complex 1 in Liver of Freeze Tolerant wood frogs, Rana sylvatica

Abstract

Many organisms experience seasonal cold environments during their life and need specific adaptations to allow them to survive when the ambient temperature fall below 0 °C. Previous studies showed a high survival rate (∼100%) of wood frog during different conditions of freezing exposure (various time and/or temperature freezing, and developmental stages of the animals). In order to balance ATP synthesis and consumption under the cold condition, optional yet energy expensive processes such as cell growth need to be suppressed or inhibited. The rate-limiting step of mRNA translation is the initiation stage, which largely regulated by the kinase complex mTORC1 (mTOR complex 1). Active mTORC1 phosphorylates the translation inhibitor 4EBP (eIF4E binding protein) and promoter S6K (40S ribosomal protein S6 kinase). Hyperphosphorylation of 4EBP inhibits its interaction with eIF4E, thereby relieving the inhibitory effect on translation pre-initiation complex assembly. Phosphorylated S6K by mTORC1 is able to enhance the RNA helicase activity of eIF4A by phosphorylating eIF4B, to clear the inhibitory secondary structures of mRNA for translation initiation machinery to reach start codon.