Phospholipid Scramblase 3 Is the Mitochondrial Target of Protein Kinase C {delta}-induced Apoptosis

Protein kinase C (PKC) δ translocates to mitochondria during apo-ptosis,but its mitochondrial target remains unclear. We found that PKC-δ physically interacted with and phosphorylated phospholipid scramblase 3 (PLS3) after UV irradiation. PLS3 is a high-affinity substrate for PKC-δ 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-δ 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-δ in the mitochondria.