Ceramide induces release of pro-apoptotic proteins from mitochondria by either a Ca2+ -dependent or a Ca2+ -independent mechanism.
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.
Di Paola
Marco
M
Institute of Biomembranes and Bioenergetics, Consiglio Nazionale delle Ricerche, Bari, Italy.
Zaccagnino
Patrizia
P
Montedoro
Grazia
G
Cocco
Tiziana
T
Lorusso
Michele
M
D000818:Animals; D001059:Apoproteins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002518:Ceramides / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009997:Osmotic Pressure / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D001059:Apoproteins; D002518:Ceramides; D024101:Mitochondrial Proteins; D002118:Calcium