Metabolic Regulation of Sodium-calcium Exchange by Intracellular Acyl CoAs

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Sep 16

PMID 16977318

Citations 23

Authors

Michael J Riedel

Istvan Baczko

Gavin J Searle

Nicola Webster

Matthew Fercho

Lynn Jones

Jessica Lang

Jonathan Lytton

Jason R B Dyck

Peter E Light

Affiliations

Soon will be listed here.

Abstract

The sodium-calcium exchanger (NCX) is a critical mediator of calcium homeostasis. In the heart, NCX1 predominantly operates in forward mode to extrude Ca(2+); however, reverse-mode NCX1 activity during ischemia/reperfusion (IR) contributes to Ca(2+) loading and electrical and contractile dysfunction. IR injury has also been associated with altered fat metabolism and accumulation of long-chain acyl CoA esters. Here, we show that acyl CoAs are novel, endogenous activators of reverse-mode NCX1 activity, exhibiting chain length and saturation dependence, with longer chain saturated acyl moieties being the most effective NCX1 activators. These results implicate dietary fat composition as a plausible determinant of IR injury. We further show that acyl CoAs may interact directly with the XIP (exchanger inhibitory peptide) sequence, a known region of anionic lipid modulation, to dynamically regulate NCX1 activity and Ca(2+) homeostasis. Additionally, our findings have broad implications for the coupling of Ca(2+) homeostasis to fat metabolism in a variety of tissues.

Citing Articles

F-NMR Probing of Ion-Induced Conformational Changes in Detergent-Solubilized and Nanodisc-Reconstituted NCX_Mj.

Nguyen K, Strauss T, Refaeli B, Hiller R, Vinogradova O, Khananshvili D Int J Mol Sci. 2024; 25(13).

PMID: 39000018 PMC: 11241019. DOI: 10.3390/ijms25136909.

The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat.

Souri F, Badavi M, Dianat M, Mard A, Sarkaki A, Razliqi R Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(7):5207-5217.

PMID: 38252301 DOI: 10.1007/s00210-024-02949-4.

Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.

Khananshvili D Int J Mol Sci. 2023; 24(1).

PMID: 36613523 PMC: 9820601. DOI: 10.3390/ijms24010061.

The Contribution of Lipotoxicity to Diabetic Kidney Disease.

Schelling J Cells. 2022; 11(20).

PMID: 36291104 PMC: 9601125. DOI: 10.3390/cells11203236.

Calcium Homeostasis in Ventricular Myocytes of Diabetic Cardiomyopathy.

Al Kury L J Diabetes Res. 2020; 2020:1942086.

PMID: 33274235 PMC: 7683117. DOI: 10.1155/2020/1942086.

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