Iron deprivation induces apoptosis via mitochondrial changes related to Bax translocation.
In order to elucidate the mechanisms involved in apoptosis induction by iron deprivation, we compared cells sensitive (38C13) and resistant (EL4) to apoptosis induced by iron deprivation. Iron deprivation was achieved by incubation in a defined iron-free medium. We detected the activation of caspase-3 as well as the activation of caspase-9 in sensitive cells but not in resistant cells under iron deprivation. Iron deprivation led to the release of cytochrome c from mitochondria into the cytosol only in sensitive cells but it did not affect the cytosolic localization of Apaf-1 in both sensitive and resistant cells. The mitochondrial membrane potential (Deltapsi(m)) was dissipated within 24 h in sensitive cells due to iron deprivation. The antiapoptotic Bcl-2 protein was found to be associated with mitochondria in both sensitive and resistant cells and the association did not change under iron deprivation. On the other hand, under iron deprivation we detected translocation of the proapoptotic Bax protein from the cytosol to mitochondria in sensitive cells but not in resistant cells. Taken together, we suggest that iron deprivation induces apoptosis via mitochondrial changes concerning proapoptotic Bax translocation to mitochondria, collapse of the mitochondrial membrane potential, release of cytochrome c from mitochondria, and activation of caspase-9 and caspase-3.
Koc
M
M
Cell Growth Control Laboratory, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeñská 1083, Prague, Czech Republic.
Nad'ová
Z
Z
Truksa
J
J
Ehrlichová
M
M
Kovár
J
J
D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005434:Flow Cytometry; D007501:Iron / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000473:pathology*; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species; D013347:Subcellular Fractions; D013997:Time Factors
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; D003470:Culture Media; D011506:Proteins; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D007501:Iron; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases