Figure 8: Model for regulation of KLF15, BCAAs, and the urea cycle by mitochondrial Ca²⁺ signaling.

Our data suggest that under conditions of low uniporter function in the liver cells, high KLF15 levels stimulate expression of BCAA catabolism pathway genes and OTC. Activation of this pathway helps maintain NADH/NAD⁺ balance. Increased uniporter activity, as observed in FLC, inhibits KLF15, leading to decreased BCAA catabolism enzyme and OTC expression. This inhibition conserves BCAAs for translation and cell growth. MCU inhibition also causes urea cycle impairment, which can lead to hyperammonemia. How the uniporter regulates KLF15 expression is not known.