A Model of Mitochondrial O2 Consumption and ATP Generation in Rat Proximal Tubule Cells.

The objective of this study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between QO2, ATP formation (GATP), ATP hydrolysis (QATP), and Na+ transport in the PT. The present model correctly predicts in vitro and in vivo measurements of QO2, GATP, and ATP and Pi concentrations in PT cells. Our simulations suggest that O2 levels are not rate-limiting in the proximal convoluted tubule absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the GATP/QO2 ratio, a key determinant of the number of Na+ moles actively reabsorbed per mole of O2 consumed. An isolated increase in QATP or in cytoplasmic pH raises GATP/QO2. Thus, variations in Na+ reabsorption and pH along the PT may, per se, generate axial heterogeneities in the efficiency of mitochondrial metabolism and Na+ transport. Our results also indicate that GATP/QO2 is strongly impacted not only by the H+ leak permeability, which reflects mitochondrial uncoupling, but also by K+ leak pathways. Simulations suggest that the negative impact of increased uncoupling in the diabetic kidney on mitochondrial metabolic efficiency is partly counterbalanced by increased rates of Na+ transport and ATP consumption. This model provides a framework to investigate the role of mitochondrial dysfunction in acute and chronic renal diseases. PMID: 31790302 [PubMed -...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research