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Sphingosine Forms Channels in Membranes That Differ Greatly from Those Formed by Ceramide

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Abstract

Ceramide channels formed in the outer membrane of mitochondria have been proposed to be the pathways by which proapoptotic proteins are released from mitochondria during the early stages of apoptosis. We report that sphingosine also forms channels in membranes, but these differ greatly from the large oligomeric barrel-stave channels formed by ceramide. Sphingosine channels have short open lifetimes and have diameters less than 2 nm, whereas ceramide channels have long open lifetimes, enlarge in size reaching diameters in excess of 10 nm. Unlike ceramide, sphingosine forms channels in erythrocyte plasma membranes that vary in size with concentration, but with a maximum possible channel diameter of 2 nm. In isolated mitochondria, a large proportion of the added sphingosine was rapidly metabolized to ceramide in the absence of externally added fatty acids or fatty-acyl-CoAs. The ceramide synthase inhibitor, fumonisin B1 failed to prevent sphingosine metabolism to ceramide and actually increased it. However, partial inhibition of conversion to ceramide was achieved in the presence of ceramidase inhibitors, indicating that reverse ceramidase activity is at least partially responsible for sphingosine metabolism to ceramide. A small amount of cytochrome c release was detected. It correlated with the level of ceramide converted from sphingosine. Thus, sphingosine channels, unlike ceramide channels, are not large enough to allow the passage of proapoptotic proteins from the intermembrane space of mitochondria to the cytoplasm.

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Abbreviations

AIF:

apoptosis inducing factor

MAC:

mitochondrial apoptosis-induced channel

pS:

picoSiemens

nS:

nanoSiemens

DiPyPC:

diphytanoylphosphatidylcholine

FB1:

fumonisin B1

OE:

N-oleylethanolamide

MAPP:

D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol

BSA:

bovine serum albumin

DNP:

2,4-dinitrophenol

PIPES:

piperazine-N,N′-bis[2-ethanesulfonic acid]

TLC:

thin layer chromatography

C16-ceramide:

N-hexadecyl-D-erythro-sphingosine

PT:

permeability transition

VDAC:

voltage dependent anion-selective channel

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Authors and Affiliations

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

    Leah J. Siskind, Sharon Fluss, Minh Bui & Marco Colombini

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  1. Leah J. Siskind
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  2. Sharon Fluss
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  3. Minh Bui
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  4. Marco Colombini
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Correspondence to Marco Colombini.

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Siskind, L.J., Fluss, S., Bui, M. et al. Sphingosine Forms Channels in Membranes That Differ Greatly from Those Formed by Ceramide. J Bioenerg Biomembr 37, 227–236 (2005). https://doi.org/10.1007/s10863-005-6632-2

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  • DOI: https://doi.org/10.1007/s10863-005-6632-2

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