Regulation of cellular anabolism by mTOR: or how I learned to stop worrying and love translation

Abstract

The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel, and often experience significant overlap in upstream and downstream a signal transduction. Despite this complexity, single pathway or even single protein activations are commonly used to extrapolate broad characterizations of cellular metabolism. Furthermore, multiple routes for peptide-chain translation initiation exist, some of which may be either exclusive or overlapping depending on the state and environment of the cell. While it may be highly impractical to account for every aspect of metabolic regulation and permutation of mRNA translation, it is important to acknowledge that investigations relating to these pathways are often incomplete and not necessarily indicative of the overall metabolic status. This becomes urgent when considering the role that cellular anabolism plays in both healthy cellular functions and the aetiology of several disease's altered metabolisms. This review describes recent advances in the understanding of cellular metabolic regulation, with specific focus given to the complexity of 'downstream' mRNA translation initiation through both mTOR-dependent and mTOR-independent signallings.

Keywords: Anabolism; Cap-dependent translation; Cap-independent translation; Protein synthesis; Translation.