Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs

Michael J. Riedel, I. Baczkó, Gavin J. Searle, Nicola Webster, Matthew Fercho, Lynn Jones, Jessica Lang, Jonathan Lytton, Jason R B Dyck, Peter E. Light

Research output: Article

31 Citations (Scopus)

Abstract

The sodium-calcium exchanger (NCX) is a critical mediator of calcium homeostasis. In the heart, NCX1 predominantly operates in forward mode to extrude Ca2+; however, reverse-mode NCX1 activity during ischemia/reperfusion (IR) contributes to Ca2+ 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 Ca2+ homeostasis. Additionally, our findings have broad implications for the coupling of Ca2+ homeostasis to fat metabolism in a variety of tissues.

Original languageEnglish
Pages (from-to)4605-4614
Number of pages10
JournalEMBO Journal
Volume25
Issue number19
DOIs
Publication statusPublished - okt. 4 2006

Fingerprint

Metabolism
Homeostasis
Sodium
Fats
Sodium-Calcium Exchanger
Calcium
Reperfusion Injury
Acyl Coenzyme A
Dietary Fats
Chain length
Esters
Modulation
Tissue
Lipids
Reperfusion
Ischemia
Chemical analysis
exchanger inhibitory peptide

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Riedel, M. J., Baczkó, I., Searle, G. J., Webster, N., Fercho, M., Jones, L., ... Light, P. E. (2006). Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. EMBO Journal, 25(19), 4605-4614. https://doi.org/10.1038/sj.emboj.7601321

Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. / Riedel, Michael J.; Baczkó, I.; Searle, Gavin J.; Webster, Nicola; Fercho, Matthew; Jones, Lynn; Lang, Jessica; Lytton, Jonathan; Dyck, Jason R B; Light, Peter E.

In: EMBO Journal, Vol. 25, No. 19, 04.10.2006, p. 4605-4614.

Research output: Article

Riedel, MJ, Baczkó, I, Searle, GJ, Webster, N, Fercho, M, Jones, L, Lang, J, Lytton, J, Dyck, JRB & Light, PE 2006, 'Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs', EMBO Journal, vol. 25, no. 19, pp. 4605-4614. https://doi.org/10.1038/sj.emboj.7601321
Riedel MJ, Baczkó I, Searle GJ, Webster N, Fercho M, Jones L et al. Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. EMBO Journal. 2006 okt. 4;25(19):4605-4614. https://doi.org/10.1038/sj.emboj.7601321
Riedel, Michael J. ; Baczkó, I. ; Searle, Gavin J. ; Webster, Nicola ; Fercho, Matthew ; Jones, Lynn ; Lang, Jessica ; Lytton, Jonathan ; Dyck, Jason R B ; Light, Peter E. / Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. In: EMBO Journal. 2006 ; Vol. 25, No. 19. pp. 4605-4614.
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