The Role of Energy Regulation in the Tubular Epithelial Cell Response to Sepsis.

Sepsis is considered today a major public health problem. Despite that mortality has been consistently associated with organ compromise, the mechanisms by which sepsis causes multiple organ dysfunction are not well understood, and hence, therapy remains reactive and non-specific. Recent studies have challenged previous paradigms by demonstrating that acute kidney injury can occur in the setting of a normal or an even increased renal blood flow, and that it is characterized by tubular injury and not by necrosis or apoptosis. This finding suggests that mechanisms other than hypoperfusion may be at play, and that adaptive responses of the tubular epithelial cell may be key to understanding the origin of organ dysfunction in the setting of sepsis. In this review, we discuss evidence suggesting that the activation of energy regulatory processes and mitochondrial quality control processes may not only be drivers of this response, but also be factors that may alter the course of organ dysfunction during sepsis in clinically relevant ways.