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Dihydroceramide hinders ceramide channel formation: Implications on apoptosis

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Abstract

Early in apoptosis, ceramide levels rise and the mitochondrial outer membrane becomes permeable to small proteins. The self-assembly of ceramide to form channels could be the means by which intermembrane space proteins are released to induce apoptosis. Dihydroceramide desaturase converts dihydroceramide to ceramide. This conversion may be removing an inhibitor as well as generating a pro-apoptotic agent. We report that both long and short chain dihydroceramides inhibit ceramide channel formation in mitochondria. One tenth as much dihydroceramide was sufficient to inhibit the permeabilization of the outer membrane by about 95% (C2) and 51% (C16). Similar quantities inhibited the release of carboxyfluorescein from liposomes indicating that other mitochondrial components are not necessary for the inhibition. The apoptogenic activity of ceramide may thus depend on the ceramide to dihydroceramide ratio resulting in a more abrupt transition from the normal to the apoptotic state when the de novo pathway is used in mitochondria.

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Abbreviations

CF:

carboxyfluorescein

C2-ceramide:

N-acetyl-D-erythro-sphingosine

C16-ceramide:

N-palmitoyl-D-erythro-sphingosine

DHC2 :

N-acetyl-D-erythro-sphinganine or C2-dihydroceramide

DHC16 :

N-palmitoyl-erythro-sphinganine or C16-dihydroceramide

DPX:

p-xylene-bis-pyridinium bromide

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Authors and Affiliations

  1. Department of Biology, University of Maryland, College Park, Maryland, 20742

    J. Stiban, D. Fistere & M. Colombini

  2. Department of Biology, University of Maryland, College Park, MD, 20742

    M. Colombini

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  1. J. Stiban
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  2. D. Fistere
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  3. M. Colombini
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Correspondence to M. Colombini.

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Stiban, J., Fistere, D. & Colombini, M. Dihydroceramide hinders ceramide channel formation: Implications on apoptosis. Apoptosis 11, 773–780 (2006). https://doi.org/10.1007/s10495-006-5882-8

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