Translocation of Bax and Bid to mitochondria, endoplasmic reticulum and nuclear envelope: possible control points in apoptosis.
The cross-talk between endoplasmic reticulum (ER) and mitochondria was investigated during apoptosis in a breast cancer cell line (MCF-7) in culture. The effect of camptothecin, an inducer of apoptosis and a specific inhibitor of topoisomerase I, was investigated by morphological, immunocytochemical and histochemical techniques for electron microscopy. Our ultrastructural morphological data demonstrate alterations in ER configuration and communication with neighbouring mitochondria early after stimulation by camptothecin. Immunoelectron studies have demonstrated that Bax and Bid translocate from cytoplasm to mitochondria where they initiate mitochondrial dysfunction and cytochrome c release. Bax and Bid were also localized in ER and nuclear envelope. Since ER and mitochondria function as intracellular Ca2+ storage, we hypothesize that Bax and Bid are involved in the emptying of ER Ca2+ pool, triggers secondary changes in mitochondrial Ca2+ levels that contribute to cytochrome c release and cell death.
Laboratory of Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, 5 Pawiński Street, 02 106 Warsaw, Poland.
Barbara
B
Gajkowska
Urszula
U
Wojewódzka
Joanna
J
Gajda
D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D001943:Breast Neoplasms / Q000737:chemistry / Q000276:immunology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000032:analysis / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D002118:Calcium; D002166:Camptothecin