Figure 9.

Proposed working model of acidosis-driven AKI in the PT. (A) PT cells take up fatty acids (FAs) from the blood via basolateral organic transporters. Peroxisomes (Per) also generate FAs, which are normally metabolized in mitochondria via complex II to generate ATP. Excess FAs can be converted to phospholipids and sphingolipids, and stored in specialized MLBs. (B) In response to acidosis, uptake and metabolism of glutamine (Gln) increases dramatically to generate ammonia (NH₃). Complex I activity also increases to provide oxidized NAD required for ammoniagenesis, which leads to a decrease in FA oxidation, enlargement of MLBs, and defects in solute uptake. Thus, prioritization of ammoniagenesis leads to functional AKI. Schematic image was produced using scientific illustration toolkits from Motifolio. FAO, fatty acid oxidation.