Constitutive presence of cytochrome c in the cytosol of a chemoresistant leukemic cell line

• Published in: Apoptosis (London) Vol. 10; no. 2; pp. 277 - 287
• Main Authors: Oliver, L, LeCabellec, M-T, Pradal, G, Meflah, K, Kroemer, G, Vallette, F M
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.03.2005
• Subjects: Apoptosis; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Proliferation; Cells; Cytochromes c - metabolism; Cytosol - metabolism; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins - metabolism; K562 Cells; Leukemia - metabolism; Microscopy, Confocal; Microscopy, Electron; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Polymerase Chain Reaction; Proto-Oncogene Proteins c-bcl-2 - metabolism; Time Factors; Transfection
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1007/s10495-005-0802-x

The release of holocytochrome c (cyt c) from mitochondria into the cytosol is reportedly a landmark of the execution phase of apoptosis. As shown here, the P-glycoprotein- (P-gp) expressing K562/ADR cell line (but not the parental K562 cell line) exhibits both cytosolic and mitochondrial cyt c in the absence of any signs of apoptosis. K562/ADR cells were found to be relatively resistant to a variety of different inducers of apoptosis, and blocking the P-gp did not reverse this resistance. The release of cyt c in non-apoptotic K562/ADR cells was not accompanied by that of any other mitochondrial apoptogenic protein, such as AIF or Smac/DIABLO, and was inhibited by Bcl-2 over expression. In addition, using a cell-free system, we show that mitochondria isolated from K562/ADR cells spontaneously released cyt c. These data suggest that cyt c release may be compatible with the preservation of mitochondrial integrity and function, as well as cell proliferation.