Mitochondrial pathway of apoptosis is ancestral in metazoans

被引:89
作者
Bender, Cheryl E. [2 ,3 ]
Fitzgerald, Patrick [1 ]
Tait, Stephen W. G. [4 ]
Llambi, Fabien [1 ]
McStay, Gavin P. [1 ]
Tupper, Douglas O. [5 ]
Pellettieri, Jason [6 ]
Alvarado, Alejandro Sanchez [7 ,8 ]
Salvesen, Guy S. [2 ]
Green, Douglas R. [1 ]
机构
[1] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Burnham Inst Med Res, Apoptosis & Cell Death Program, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA
[4] Univ Glasgow, Beatson Inst Canc Res, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland
[5] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
[6] Keene State Coll, Keene, NH 03435 USA
[7] Howard Hughes Med Inst, Kansas City, MO 64110 USA
[8] Stowers Inst Med Res, Kansas City, MO 64110 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
PROGRAMMED CELL-DEATH; CYTOCHROME-C; CASPASE ACTIVATION; DROSOPHILA-MELANOGASTER; UNIFIED MODEL; PROTEIN; APAF-1; BAK; PROCASPASE-9; CLEAVAGE;
D O I
10.1073/pnas.1120680109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome c, which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. Here we show that apoptosis in a lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and that cytochrome c triggers caspase activation in cytosolic extracts from these animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate MOMP. These results suggest that the mitochondrial pathway of apoptosis in animals predates the emergence of the vertebrates but was lost in some lineages (e.g., nematodes). In further support of this hypothesis, we surveyed the ability of cytochrome c to trigger caspase activation in cytosolic extracts from a variety of organisms and found this effect in cytosolic extracts from invertebrate deuter-ostomes (phylum Echinodermata).
引用
收藏
页码:4904 / 4909
页数:6
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