Truncating PKHD1 and PKD2 mutations alter energy metabolism.

Truncating PKHD1 and PKD2 mutations alter energy metabolism. Am J Physiol Renal Physiol. 2018 Dec 19;: Authors: Chumley P, Zhou J, Mrug S, Chacko BK, Parant JM, Challa AK, Wilson LS, Berryhill TF, Barnes S, Kesterson RA, Bell PD, Darley-Usmar VM, Yoder BK, Mrug M Abstract Deficiency in polycystin 1 triggers specific changes in energy metabolism. To determine whether defects in other human cystoproteins have similar effects, we studied extracellular acidification and glucose metabolism in HEK293 cell lines with PKHD1 and PKD2 truncating defects along multiple sites of truncating mutations found in patients with autosomal recessive and dominant polycystic kidney diseases (ARPKD and ADPKD). While the PKHD1 or PKD2 gene mutations or their position had no overall effect on cell proliferation rate in our cell line models, truncating mutations in these genes progressively increased overall extracellular acidification over time (p<0.001 for PKHD1 and PKD2 mutations). PKHD1 mutations increased non-glycolytic acidification rate (1.19 vs 1.03; p=0.002), consistent with an increase in tricarboxylic acid (TCA) cycle activity or breakdown of intracellular glycogen. In addition, they increased basal and ATP-linked oxygen consumption rates (7.59 vs 5.42; p=0.015 and 4.55 vs 2.98, p=0.004). Together with previous studies of polycystin 1 deficiency, these data suggest that defects in major PKD genes trigger changes in energy metabolism. Following v...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research