Apoptosis triggered redistribution of caspase-9 from cytoplasm to mitochondria.
Caspase-9 is an apoptosis initiator protease activated as a response to the mitochondrial damage in the cytoplasmic complex apoptosome. By fluorescence labelling of proteins, confocal microscopy and subcellular fractionations we demonstrate that caspase-9 is in the cytoplasm of non-apoptotic pituitary cells. The activation of apoptosis with rotenone triggers the redistribution of caspase-9 to mitochondria. Experiments using the general caspase inhibitor z-VAD.fmk and the specific caspase-9 inhibitor z-LEHD.fmk show that the caspase-9 redistribution is a regulated process and requires the activity of a caspase other than the caspase-9. We propose that this spatial regulation is required to control the activity of caspase-9.
Potokar
M
M
Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Medical Faculty Ljubljana, Zaloska 4, Slovenia.
Milisav
I
I
Kreft
M
M
Stenovec
M
M
Zorec
R
R
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D013347:Subcellular Fractions; D014162:Transfection
D000590:Amino Acid Chloromethyl Ketones; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D012402:Rotenone; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases