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Phospholipid Scramblase 3 Is the Mitochondrial Target of Protein Kinase C -induced Apoptosis¹

Huntsman Cancer Institute and Section of Oncology, Department of Medicine, University of Utah, Salt Lake City, Utah 84112

Protein kinase C (PKC) translocates to mitochondria during apo-ptosis,but its mitochondrial target remains unclear. We found that PKC- physically interacted with and phosphorylated phospholipid scramblase 3 (PLS3) after UV irradiation. PLS3 is a high-affinity substrate for PKC- in vitro with the K_m at 10.5 nM. Cells expressing wild-type PLS3 became apoptotic on phorbol ester stimulation, whereas the control cells did not. Expression of a mitochondrial-targeted PKC- enhanced apoptosis more prominently in HeLa-PLS3 cells than control HeLa cells and HeLa cells expressing an inactive PLS3 mutant. These results indicate that PLS3 is a downstream effector of PKC- in the mitochondria.

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