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. Author manuscript; available in PMC: 2022 Apr 1.
Published in final edited form as: Crit Care Clin. 2021 Feb 13;37(2):279–301. doi: 10.1016/j.ccc.2020.11.010

Figure 2. Metabolic Reprogramming.

Figure 2.

In the early metabolic response to S-AKI, renal tubular epithelial cells undergo a proinflammatory phase (acute anabolic phase) metabolism in which the Akt/mammalian target of rapamycin complex 1 (mTORC1)/Hypoxia Inducible Factor (HIF)-1α complex drives the induction of aerobic glycolysis by increasing the expression of glycolytic enzymes (e.g. lactate dehydrogenase [LDH], PKM2 and pyruvate dehydrogenase kinase [PDHK]). HIF-1α promotes the conversion of pyruvate to lactate and, along with PDHK, inhibit the conversion of lactate into acetyl-CoA hindering the induction of the Krebs cycle and decreasing OXPHOS. In the late anti-inflammatory (adaptive catabolic phase) OXPHOS, metabolic pathways are reestablished. This is driven by adenosine monophosphate-activated protein kinase (AMPK) activation, Sirt1 and Sirt6. AMPK activates Sirt1 and Sirt6. Sirt6 will block the activity of HIF-1α switching back from aerobic glycolysis to OXPHOS. is induced by the decrease in ATP levels. AMPK activates peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC)-1α and with CPT-1 will stimulate fatty acid oxidation and oxidative metabolism. Furthermore, PGC1α along with AMPK will induce mitochondrial biogenesis.17,36,50

Adopted and adapted from: Gómez, H., Kellum, J. A. & Ronco, C. Metabolic reprogramming and tolerance during sepsis-induced AKI. Nature Reviews Nephrology 13, 143, doi:10.1038/nrneph.2016.186 (2017).