Mitochondrial trafficking and redox/phosphorylation signaling supporting cell migration phenotypes

Abstract

Regulation of cell signaling cascades is critical in making sure the response is activated spatially and for a desired duration. Cell signaling cascades are spatially and temporally controlled through local protein phosphorylation events which are determined by the activation of specific kinases and/or inactivation of phosphatases to elicit a complete and thorough response. For example, A-kinase-anchoring proteins (AKAPs) contribute to the local regulated activity protein kinase A (PKA). The activity of kinases and phosphatases can also be regulated through redox-dependent cysteine modifications that mediate the activity of these proteins. A primary example of this is the activation of the epidermal growth factor receptor (EGFR) and the inactivation of the phosphatase and tensin homologue (PTEN) phosphatase by reactive oxygen species (ROS). Therefore, the local redox environment must play a critical role in the timing and magnitude of these events. Mitochondria are a primary source of ROS and energy (ATP) that contributes to redox-dependent signaling and ATP-dependent phosphorylation events, respectively. The strategic positioning of mitochondria within cells contributes to intracellular gradients of ROS and ATP, which have been shown to correlate with changes to protein redox and phosphorylation status driving downstream cellular processes. In this review, we will discuss the relationship between subcellular mitochondrial positioning and intracellular ROS and ATP gradients that support dynamic oxidation and phosphorylation signaling and resulting cellular effects, specifically associated with cell migration signaling.

Keywords: cell migration; focal adhesion (FA); mitochondrial trafficking; phosphorylation; redox signaling.