Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis
文献类型：期刊论文
| 作者 | Zhao, Kai1; Zhou, Hejiang1,2; Zhao, Xingyu1; Wolff, Dennis W.3; Tu, Yaping1,3; Liu, Huili4; Wei, Taotao1; Yang, Fuyu1 |
| 刊名 | JOURNAL OF LIPID RESEARCH
 |
| 出版日期 | 2012-10-01 |
| 卷号 | 53期号:10页码:2102-2114 |
| 关键词 | Bid chymotrypsin lysosome enzymology |
| 英文摘要 | Upon apoptotic stimuli, lysosomal proteases, including cathepsins and chymotrypsin, are released into cytosol due to lysosomal membrane permeabilization (LMP), where they trigger apoptosis via the lysosomal-mitochondrial pathway of apoptosis. Herein, the mechanism of LMP was investigated. We found that caspase 8-cleaved Bid (tBid) could result in LMP directly. Although Bax or Bak might modestly enhance tBid-triggered LMP, they are not necessary for LMP. To study this further, large unilamellar vesicles (LUVs), model membranes mimicking the lipid constitution of lysosomes, were used to reconstitute the membrane permeabilization process in vitro. We found that phosphatidic acid (PA), one of the major acidic phospholipids found in lysosome membrane, is essential for tBid-induced LMP. PA facilitates the insertion of tBid deeply into lipid bilayers, where it undergoes homo-oligomerization and triggers the formation of highly curved nonbilayer lipid phases. These events induce LMP via pore formation mechanisms because encapsulated fluorescein-conjugated dextran (FD)-20 was released more significantly than FD-70 or FD-250 from LUVs due to its smaller molecular size. On the basis of these data, we proposed tBid-PA interactions in the lysosomal membranes form lipidic pores and result in LMP. We further noted that chymotrypsin-cleaved Bid is more potent than tBid at binding to PA, inserting into the lipid bilayer, and promoting LMP. This amplification mechanism likely contributes to the culmination of apoptotic signaling. Zhao, K., H. Zhou, X. Zhao, D. W. Wolff, Y. Tu, H. Liu, T. Wei, and F. Yang. Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis. J. Lipid Res. 2012. 53: 2102-2114. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | MITOCHONDRIAL OUTER-MEMBRANE ; LIPIDIC PORE FORMATION ; CELL-DEATH ; LYSOPHOSPHATIDIC ACID ; CYTOCHROME-C ; OLIGOMERIZES BAK ; BINDING-ACTIVITY ; BCL-2 FAMILY ; CARDIOLIPIN ; PROTEIN |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000308696600010 |
| 公开日期 | 2015-07-14 |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/1562]  |
| 专题 | 武汉物理与数学研究所_高技术创新与发展中心 |
| 作者单位 | 1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China 3.Creighton Univ, Sch Med, Dept Pharmacol, Omaha, NE 68178 USA 4.Chinese Acad Sci, Wuhan Inst Phys & Math, Wuhan Ctr Magnet Resonance, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhao, Kai,Zhou, Hejiang,Zhao, Xingyu,et al. Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis[J]. JOURNAL OF LIPID RESEARCH,2012,53(10):2102-2114. |
| APA | Zhao, Kai.,Zhou, Hejiang.,Zhao, Xingyu.,Wolff, Dennis W..,Tu, Yaping.,...&Yang, Fuyu.(2012).Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis.JOURNAL OF LIPID RESEARCH,53(10),2102-2114. |
| MLA | Zhao, Kai,et al."Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis".JOURNAL OF LIPID RESEARCH 53.10(2012):2102-2114. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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