Figure 3. Metabolic Adaptive Response to Sepsis: Prioritizing Cell Survival.

As consequence of the early metabolic reprogramming that TEC undergoes during sepsis, non-vital functions such as cell replication, protein synthesis and ion transportation are put in ‘stand-by’, and the limited amount of ATP available is redirected toward vital functions, prioritizing cell survival at the expense of cell function. Active transport pumps such as Na⁺/K⁺ ATPase are engulfed by the cell to limit the spend of ATP. Additionally, one of the most cell energy-consuming processes is cell replication. TEC have intrinsic mechanisms that allow to detect if the cell possesses enough ATP to undergo a complete cell cycle. If this is not the case it would shut down cell replication, resulting in elevation of cycle arrest biomarkers (i.e. IGFBP7 and TIMP2). Finally, to restore TEC oxidative metabolism and normal TEC metabolism, a healthy pool of mitochondria is required. During sepsis, mitochondrial population is severely injured. As a protective mechanism, mitochondrial quality control processes such as mitophagy and biogenesis are activated as a mechanism to restore the mitochondrial pool and switch back to OXPHOS.

Adopted and adapted from: Peerapornratana, S., Manrique-Caballero, C. L., Gómez, H. & Kellum, J. A. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney international 96, 1083–1099, doi:10.1016/j.kint.2019.05.026 (2019).