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PMID: 16977318 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs.

The EMBO journal ·Vol. 25 ·No. 19 ·2006-10-04 ·Pages 4605-14

Riedel MJ, Baczkó I, Searle GJ, Webster N, Fercho M, Jones L, Lang J, Lytton J, Dyck JR, Light PE

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.

MeSH Terms
Acyl Coenzyme A/metabolism Adenosine Triphosphate/metabolism Animals Animals, Newborn Calcium/metabolism Cells, Cultured Fatty Acids/metabolism Heart Ventricles/metabolism Male Myocytes, Cardiac/metabolism Peptides/metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Rats Rats, Sprague-Dawley Sodium-Calcium Exchanger/metabolism
Chemicals
Acyl Coenzyme A Fatty Acids Peptides Phosphatidylinositol 4,5-Diphosphate Sodium-Calcium Exchanger sodium-calcium exchanger 1 exchanger inhibitory peptide Adenosine Triphosphate Calcium
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Riedel Michael J
Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
Baczkó István
Searle Gavin J
Webster Nicola
Fercho Matthew
Jones Lynn
Lang Jessica
Lytton Jonathan
Dyck Jason R B
Light Peter E
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601321
Published
2006-10-04
Epub
2006-00-14
Pages
4605-14
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1589979
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601321 PMC Full Text View journal details
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