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Journal of Bioenergetics and Biomembranes

, Volume 37, Issue 4, pp 227–236 | Cite as

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

  • Leah J. Siskind
  • Sharon Fluss
  • Minh Bui
  • Marco Colombini
Article

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.

Keywords

Mitochondria apoptosis sphingolipids ion channels ceramidase ceramide synthase sphingosine ceramide 

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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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Leah J. Siskind
    • 1
  • Sharon Fluss
    • 1
  • Minh Bui
    • 1
  • Marco Colombini
    • 1
  1. 1.Department of BiologyUniversity of Maryland College ParkCollege Park

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