Targeting of protein kinase C delta to mitochondria in the oxidative stress response.
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 (PKCdelta) to mitochondria. The results demonstrate that H2O2-induced activation of PKCdelta is necessary for translocation of PKCdelta from the cytoplasm to the mitochondria. The results also show that mitochondrial targeting of PKCdelta 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 PKCdelta activation and translocation to mitochondria. These findings indicate that mitochondrial targeting of PKCdelta is required, at least in part, for the apoptotic response of cells to oxidative stress.
Majumder
P K
PK
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mishra
N C
NC
Sun
X
X
Bharti
A
A
Kharbanda
S
S
Saxena
S
S
Kufe
D
D
D016475:3T3 Cells; D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D003574:Cytochrome c Group; D007527:Isoenzymes; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C497259:Prkcd protein, mouse; D016315:Proto-Oncogene Proteins c-abl; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta