Characterization of the effects of RACK1 expression on mitochondrial physiology

Abstract

Receptor for activated C kinase 1 (RACK1) is a multifunctional scaffolding protein that coordinates a variety of fundamental cellular processes in eukaryotic cells, and its aberrant expression has been implicated in the development of multiple disease states. A poorly described region of RACK1 biology is how RACK1 function interacts with mitochondrial physiology. A broad characterization of mitochondrial structure and function in the context of aberrant RACK1 signaling has yet to be completed. Therefore, the goal of this project was to characterize how a decrease in RACK1 expression impacted mitochondrial physiology in HeLa cells. RACK1 KD cells exhibited a loss of mitochondrial network connectivity, dysregulation of mediators required for mitochondrial network dynamics/biogenesis, and decreases in mitochondrial respiration/energy production. Additional stress such as nutrient depletion increased phenotype severity. These results highlight how important further characterization of the RACK1 interactome is for our understanding of its influence over cellular function.