{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:35:18Z","timestamp":1775010918549,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,1,16]],"date-time":"2007-01-16T00:00:00Z","timestamp":1168905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phospholipid scramblase 3 (PLS3) is a member of the phospholipid scramblase family present in mitochondria. PLS3 plays an important role in regulation of mitochondrial morphology, respiratory function, and apoptotic responses. PLS3 is phosphorylated by PKC\u2010\u03b4 at Thr21 and is the mitochondrial target of PKC\u2010\u03b4\u2010induced apoptosis. Cells with overexpression of PLS3, but not the phosphoinhibitory mutant PLS3(T21A), are more susceptible to apoptosis induced by AD198, an extranuclear targeted anthracycline that activates PKC\u2010\u03b4. Here we report that the phosphomimetic mutant of PLS3(T21D) by itself can induce apoptosis in HeLa cells. Using proteoliposomes with addition of pyrene\u2010labeled phosphatidylcholine (PC) at the outer leaflet, we measured the lipid flip\u2010flop activity of PLS3 and its phosphorylation mutant. PLS3(T21D) is more potent than wild\u2010type PLS3 or PLS3(T21A) to transfer pyrene\u2010PC from the outer leaflet to the inner leaflet of liposomes. Based on our previous finding that PLS3 enhances tBid\u2010induced mitochondrial damages, we tested the hypothesis that PLS3 enhances cardiolipin translocation to mitochondrial surface and facilitates tBid targeting. Fluorescein\u2010labeled tBid(G94E) was used as a probe to quantify cardiolipin on the surface of mitochondria. Mitochondria from cells treated with AD198 or cells expressing PLS3(T21D) had a higher level of tBid\u2010binding capacity than control cells or cells expressing wild\u2010type PLS3. These findings indicate that phosphorylation of PLS3 by PKC\u2010\u03b4 induces PLS3 activation to facilitate mitochondrial targeting of tBid and apoptosis. J. Cell. Biochem. 101:1210\u20131221, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.21243","type":"journal-article","created":{"date-parts":[[2007,1,16]],"date-time":"2007-01-16T23:40:54Z","timestamp":1168990854000},"page":"1210-1221","source":"Crossref","is-referenced-by-count":51,"title":["Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C\u2010\u03b4 induces its activation and facilitates mitochondrial targeting of 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