Mitochondrial TCA cycle intermediates regulate body fluid and acid-base balance
János Peti-Peterdi
János Peti-Peterdi
Published July 1, 2013; First published June 24, 2013
Citation Information: J Clin Invest. 2013;123(7):2788-2790. https://doi.org/10.1172/JCI68095.
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Commentary

Mitochondrial TCA cycle intermediates regulate body fluid and acid-base balance

Abstract

Intrarenal control mechanisms play an important role in the maintenance of body fluid and electrolyte balance and pH homeostasis. Recent discoveries of new ion transport and regulatory pathways in the distal nephron and collecting duct system have helped to better our understanding of these critical kidney functions and identified new potential therapeutic targets and approaches. In this issue of the JCI, Tokonami et al. report on the function of an exciting new paracrine mediator, the mitochondrial the citric acid (TCA) cycle intermediate α-ketoglutarate (αKG), which via its OXGR1 receptor plays an unexpected, nontraditional role in the adaptive regulation of renal HCO3– secretion and salt reabsorption.

Authors

János Peti-Peterdi

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Figure 1

Illustration of the renal expression and functions of mitochondrial TCA cycle intermediates in the regulation of body fluid and acid-base balance.

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Illustration of the renal expression and functions of mitochondrial TCA ...
In addition to the collecting duct, Sucnr1 is expressed in the macula densa (MD) segment of the distal nephron and mediates succinate-induced renin release from the adjacent juxtaglomerular cell (JGC) via paracrine signaling. αKG in the tubular fluid mediates a paracrine crosstalk between proximal and distal nephron segments. Via OXGR1 expressed in type B (and also in non-A–non-B) intercalated cells (ICs) of the distal nephron and collecting duct, αKG regulates HCO3– secretion and electroneutral transepithelial NaCl reabsorption. These intrarenal mechanisms appear to play important new roles in the regulation of body fluid and electrolyte balance and acid-base homeostasis. Adapted with permission from Physiology (12). RAS, renin-angiotensin system.