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Data from: Redox state of NAD modulates the activation of Na-bicarbonate cotransporter NBCe1-B by IRBIT and L-IRBIT

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Mar 22, 2024 version files 155.89 KB

Abstract

NAD is known as a coenzyme for many enzymes catalyzing redox reactions or as a substrate for enzymes for second messenger cADP-ribose generation or protein deacetylation. IRBIT and L-IRBIT are structurally conserved with dehydrogenases but lacking catalytic activity. By protein interaction, the IRBITs instead modulate many proteins of fundamental biological importance. Among these is the Na+-HCO3− cotransporter NBCe1-B, which plays a central role in intracellular pH (pHi) regulation and epithelial electrolyte transport. Here, we demonstrate that NAD modulates NBCe1-B activation by serving as a cofactor of the IRBITs. Blocking NAD salvage pathway decreases NBCe1-B activation by the IRBITs. NAD+ administration enhances, whereas NADH decreases NBCe1-B activity. Our study reveals a new role of NAD and greatly expands our appreciation of NAD biology. Because NAD redox state fluctuates greatly with metabolic status, our work provides insight into how, via IRBITs, energy metabolism could affect pHi regulation and many other IRBIT-dependent processes.