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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitochondrial pathway of apoptosis is ancestral in metazoans
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Mitochondrial pathway of apoptosis is ancestral in metazoans

机译：细胞凋亡的线粒体途径在后生动物中是祖先的

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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 Platyhelminth.es), 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).
机译：凋亡的线粒体途径是脊椎动物生理细胞死亡的主要机制。在此途径中，Bcl-2家族的促凋亡成员引起线粒体外膜通透性（MOMP），从而释放细胞色素c，该色素与Apaf-1相互作用以触发caspase激活和凋亡。尽管无脊椎动物门中的Bcl-2，Apaf-1和半胱氨酸蛋白酶具有保守性，但任何无脊椎动物中线粒体途径的存在充其量是有争议的。在这里，我们表明，在光子虫，平面虫（Platyhelminth.es）中的凋亡与MOMP有关，并且细胞色素c触发了这些动物的胞质提取物中的caspase活化。此外，涡虫Bcl-2家族蛋白可以诱导和/或调节酵母中的细胞死亡，并且可以替代哺乳动物细胞中的Bcl-2蛋白来调节MOMP。这些结果表明，动物体内线粒体凋亡的途径早于脊椎动物的出现，但在某些谱系（例如线虫）中却消失了。为了进一步支持这一假设，我们调查了细胞色素c触发多种生物体的胞质提取物中caspase活化的能力，并在无脊椎动物氘代动物孔雀纲（Echinodermata）的胞质提取物中发现了这种作用。

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    Cheryl E. Bender; Patrick Fitzgerald; Stephen W. G. Tait; Fabien Llambi; Gavin P. McStay; Douglas O. Tupper; Jason Pellettieri; Alejandro Sanchez Alvarado; Guy S. Salvesen; Douglas R. Green;

  • 作者单位

    Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA 92037,Biomedical Sciences Graduate Program, University of California at San Diego, La Jolla, CA 92093;

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;

    lnstitute of Cancer Science, Beatson Institute for Cancer Research, University of Glasgow, Glasgow G61 1BD, United Kingdom;

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;

    La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;

    Keene State College, Keene, NH 03435;

    Howard Hughes Medical Institute, Kansas City, MO 64110,Stowers Institute for Medical Research, Kansas City, MO 64110;

    Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA 92037;

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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