Ceramide-induced activation of cytosolic NADH/cytochrome c electron transport pathway: An additional source of energy for apoptosis.
We have investigated whether increase in the oxidation rate of exogenous cytochrome c (cyto-c), induced by long-chain ceramides, might be due to an increased rate of cytosolic NADH/cyto-c electron transport pathway. This process was identified in isolated liver mitochondria and has been studied in our laboratory for many years. Data from highly specific test of sulfite oxidase prove that exogenous cyto-c both in the absence and presence of ceramide cannot permeate through the mitochondrial outer membrane. However, the oxidation of added NADH, mediated by exogenous cyto-c and coupled to the generation of a membrane potential supporting the ATP synthesis, can also be stimulated by ceramide. The results obtained suggest that ceramide molecules, by increasing mitochondrial permeability, with the generation of either raft-like platforms or channels, may have a dual function. They can promote the release of endogenous cyto-c and activate, with an energy conserving process, the oxidation of cytosolic NADH either inducing the formation of new respiratory contact sites or increasing the frequency of the pre-existing porin contact sites. In agreement with the data in the literature, an increase of mitochondrial ceramide molecules level may represent an efficient strategy to activate and support the correct execution of apoptotic program.
Gorgoglione
Vincenza
V
Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Palmitessa
Valeria
V
Lofrumento
Dario Domenico
DD
La Piana
Gianluigi
G
Abbrescia
Daniela Isabel
DI
Marzulli
Domenico
D
Lofrumento
Nicola Elio
NE
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002518:Ceramides / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004579:Electron Transport; D004734:Energy Metabolism; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D008933:Mitochondrial Swelling; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D051381:Rats; D050876:Sulfite Oxidase / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology
D002518:Ceramides; D009243:NAD; C097760:N-palmitoylsphingosine; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D050876:Sulfite Oxidase; D000263:Adenylate Kinase; D014357:Trypsin