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- Title
Metabolic regulation of sodium–calcium exchange by intracellular acyl CoAs.
- Authors
Riedel, Michael J.; Baczkó, István; Searle, Gavin J.; Webster, Nicola; Fercho, Matthew; Jones, Lynn; Lang, Jessica; Lytton, Jonathan; Dyck, Jason R. B.; Light, Peter E.
- 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.
- Subjects
METABOLIC regulation; HOMEOSTASIS; CALCIUM; ISCHEMIA; ESTERS; BIOCHEMISTRY
- Publication
EMBO Journal, 2006, Vol 25, Issue 19, p4605
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601321