Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations Academic Article uri icon


MeSH Major

  • Ceramides
  • Erythrocytes
  • Intracellular Membranes
  • Mitochondria, Liver
  • Mitochondrial Membranes


  • Recent evidence suggests that the ability of ceramides to induce apoptosis is due to a direct action on mitochondria. Mitochondria are known to contain enzymes responsible for ceramide synthesis and hydrolysis and mitochondrial ceramide levels have been shown to be elevated prior to the mitochondrial phase of apoptosis. Ceramides have been reported to induce the release of intermembrane space proteins from mitochondria, which has been linked to their ability to form large channels in membranes. The aim of this study was to determine if the membrane concentration of ceramide required for the formation of protein permeable channels is within the range that is present in mitochondria during the induction phase of apoptosis. Only a very small percentage of the ceramide actually inserts into the mitochondrial membranes. The permeability of the mitochondrial outer membrane correlates directly with the level of ceramide in the membrane. Importantly, the concentration of ceramide at which significant channel formation occurs is consistent with the level of mitochondrial ceramide that occurs during the induction phase of apoptosis (4 pmol ceramide/nanomole phospholipid). Similar results were obtained with short- and long-chain ceramide. Ceramide channel formation is specific to mitochondrial membranes in that no channel formation occurs in the plasma membranes of erythrocytes even at concentrations 20 times higher than those required for channel formation in mitochondrial outer membranes. Thus, ceramide channels are good candidates for the pathway by which proapoptotic proteins are released from mitochondria during the induction phase of apoptosis.

publication date

  • June 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC2246045

Digital Object Identifier (DOI)

  • 10.1016/j.mito.2006.03.002

PubMed ID

  • 16713754

Additional Document Info

start page

  • 118

end page

  • 25


  • 6


  • 3