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Cell Growth & Differentiation Vol. 12, 465-470, September 2001
© 2001 American Association for Cancer Research

Targeting of Protein Kinase C {delta} to Mitochondria in the Oxidative Stress Response1

Pradip K. Majumder, Neerad C. Mishra, Xiangao Sun, Ajit Bharti, Surender Kharbanda, Satya Saxena and Donald Kufe2

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 [P. K. M., X. S., A. B., S. K., D. K.] and Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87115 [N. C. M., S. S.]

The cellular response to oxidative stress includes the release of mitochondrial cytochrome c and the induction of apoptosis. Here we show that treatment of diverse cells with hydrogen peroxide (H2O2) induces the targeting of protein kinase C {delta} (PKC{delta}) to mitochondria. The results demonstrate that H2O2-induced activation of PKC{delta} is necessary for translocation of PKC{delta} from the cytoplasm to the mitochondria. The results also show that mitochondrial targeting of PKC{delta} is associated with the loss of mitochondrial transmembrane potential and release of cytochrome c. The functional importance of this event is also supported by the demonstration that H2O2-induced apoptosis is blocked by the inhibition of PKC{delta} activation and translocation to mitochondria. These findings indicate that mitochondrial targeting of PKC{delta} is required, at least in part, for the apoptotic response of cells to oxidative stress.




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Copyright © 2001 by the American Association of Cancer Research.