Ceramide induces release of pro-apoptotic proteins from mitochondria by either a Ca2+ -dependent or a Ca2+ -independent mechanism

J Bioenerg Biomembr. 2004 Apr;36(2):165-70. doi: 10.1023/b:jobb.0000023619.97392.0c.


Several observations have been reported in the last years indicating that ceramide may activate the mitochondrial route of apoptosis. We show here that on addition of either C2- or C16-ceramide to mitochondria isolated from rat heart and suspended in a saline medium, release of cytochrome c and apoptosis-inducing factor (AIF) from the intermembrane space takes place. The release process is Ca2+ -independent and is not inhibited by Cyclosporin A (CsA). For the protein release process to occur, the presence of an oxidizable substrate is required. When mitochondria are suspended in sucrose instead of potassium medium, only short chain C2-ceramide causes cytochrome c release through a Ca2+ -dependent and CsA sensitive mitochondrial permeability transition (MPT) mechanism. The latter effect appears to be related to the membrane potential dissipating ability exhibited by short chain C2-ceramide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoproteins / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Calcium / metabolism*
  • Cells, Cultured
  • Ceramides / pharmacology*
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism*
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Osmotic Pressure / drug effects
  • Rats
  • Rats, Wistar


  • Apoproteins
  • Ceramides
  • Mitochondrial Proteins
  • Calcium