Dynamic Mitochondrial Localisation of STAT3 in the Cellular Adipogenesis Model 3T3-L1.

ABSTRACT

A mechanistic relationship exists between protein localisation, activity and cellular differentiation. Understanding the contribution of these molecular mechanisms is required for elucidation of conditions that drive development. Literature suggests non-canonical translocation of the Signal Transducer and Activator of Transcription 3 (STAT3) to the mitochondria contributes to the regulation of the electron transport chain, cellular respiration and reactive oxygen species production. Based on this we investigated the role of mitochondrial STAT3, specifically the serine 727 phosphorylated form, in cellular differentiation using the well-defined mouse adipogenic model 3T3-L1. Relative levels of reactive oxygen species (ROS) and the levels and dynamic localization of pSTAT3S727 were investigated during the initiation of adipogenesis. As a signalling entity, ROS is known to regulate the activation of C/EBPß to stimulate a critical cascade of events prior to differentiation of 3T3-L1. Results indicate that upon induction of the differentiation programme, relative levels of mitochondrial pSTAT3S727 dramatically decrease in the mitochondria; in contrast the total cellular pSTAT3S727 levels increase. A positive correlation between increasing levels of ROS and dynamic changes in C/EBPß indicate that mitochondrial STAT3 plays a potential critical role as an initiator of the process. Based on these findings we propose a model for mitochondrial STAT3 as a regulator of ROS in adipogenesis.