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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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.[1]


  1. Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. Riedel, M.J., Baczk??, I., Searle, G.J., Webster, N., Fercho, M., Jones, L., Lang, J., Lytton, J., Dyck, J.R., Light, P.E. EMBO J. (2006) [Pubmed]
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